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Natale P, Green SC, Tunnicliffe DJ, Pellegrino G, Toyama T, Strippoli GF. Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev 2025; 2:CD015849. [PMID: 39963952 PMCID: PMC11834151 DOI: 10.1002/14651858.cd015849.pub2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Indexed: 02/21/2025]
Abstract
BACKGROUND Approximately 40% of people with diabetes develop kidney failure and experience an accelerated risk of cardiovascular complications. Glucagon-like peptide 1 (GLP-1) receptor agonists are glucose-lowering agents that manage glucose and weight control. OBJECTIVES We assessed the benefits and harms of GLP-1 receptor agonists in people with chronic kidney disease (CKD) and diabetes. SEARCH METHODS The Cochrane Kidney and Transplant Register of Studies was searched to 10 September 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA Randomised controlled studies were eligible if participants with diabetes and CKD were randomly allocated to a GLP-1 receptor agonist, placebo, standard care or a second glucose-lowering agent. CKD included all stages (from 1 to 5). DATA COLLECTION AND ANALYSIS Three authors independently extracted data and assessed the risk of bias using the risk of bias assessment tool 2. Pooled analyses using summary estimates of effects were obtained using a random-effects model, and results were expressed as risk ratios (RR) and/or hazard ratio (HR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. The primary outcomes included death (all-cause and cardiovascular), 3- and 4-point major adverse cardiovascular events (MACE), kidney failure, composite kidney outcome, and severe hypoglycaemia. The secondary outcomes included non-fatal or fatal myocardial infarction (MI) or stroke, non-fatal peripheral arterial events, heart failure, hospitalisation due to heart failure, estimated glomerular filtration rate or creatinine clearance, doubling of serum creatinine, urine albumin-to-creatinine ratio, albuminuria progression, vascular access outcomes, body weight, body mass index, fatigue, life participation, peritoneal dialysis infection, peritoneal dialysis failure, adverse events, serious adverse events, withdrawal due to adverse events, HbA1c, sudden death, acute MI, ischaemic stroke, and coronary revascularisation. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS Forty-two studies involving 48,148 participants were included. All studies were conducted on people with type 2 diabetes, and no studies were carried out on children. The median study age was 66 years. The median study follow-up was 26 weeks. Six studies were conducted in people with CKD stages 1-2, 11 studies in people with CKD stages 3-5, one study in people on dialysis, and the remaining studies included people with both CKD stages 1-2 and 3-5. Risks of bias in the included studies for all the primary outcomes in studies that compared GLP-1 receptor agonists to placebo were low in most methodological domains, except one study that was assessed at high risk of bias due to missing outcome data for death (all-cause and cardiovascular). The overall risk of bias for all-cause and cardiovascular death in studies that reported the treatment effects of GLP-1 receptor agonists compared to standard care, dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose cotransporter 2 (SGLT2) inhibitors were assessed as unclear or at high risk of bias due to deviations from intended interventions or missing data. For GLP-1 receptor agonists compared to insulin or another GLP-1 receptor agonist, the risk of bias for all-cause and cardiovascular death was low or unclear. Compared to placebo, GLP-1 receptor agonists probably reduced the risk of all-cause death (RR 0.85, 95% CI 0.74 to 0.98; I2 = 23%; 8 studies, 17,861 participants; moderate-certainty evidence), but may have little or no effect on cardiovascular death (RR 0.84, 95% CI 0.68 to 1.05; I2 = 42%; 7 studies, 17,801 participants; low-certainty evidence). Compared to placebo, GLP-1 receptor agonists probably decreased 3-point MACE (RR 0.84, 95% CI 0.73 to 0.98; I² = 65%; 4 studies, 19,825 participants; moderate-certainty evidence), and 4-point MACE compared to placebo (RR 0.77, 95% CI 0.67 to 0.89; 1 study, 2,158 participants; moderate-certainty evidence). Based on absolute risks of clinical outcomes, it is likely that GLP-1 receptor agonists prevent all-cause death in 52 people with CKD stages 1-2 and 116 in CKD stages 3-5, cardiovascular death in 34 people with CKD stages 1-2 and 71 in CKD stages 3-5, while 95 CKD stages 1-2 and 153 in CKD stages 3-5 might experience a major cardiovascular event for every 1000 people treated over 1 year. Compared to placebo, GLP-1 receptor agonists probably had little or no effect on kidney failure, defined as starting dialysis or kidney transplant (RR 0.86, 95% CI 0.66 to 1.13; I2 = 0%; 3 studies, 4,134 participants; moderate-certainty evidence), or on composite kidney outcomes (RR 0.89, 95% CI 0.78 to 1.02; I2 = 0%; 2 studies, 16,849 participants; moderate-certainty evidence). Compared to placebo, GLP-1 receptor agonists may have little or no effect on the risk of severe hypoglycaemia (RR 0.82, 95% CI 0.54 to 1.25; I2 = 44%; 4 studies, 6,292 participants; low-certainty evidence). The effects of GLP-1 receptor agonists compared to standard care or other hypoglycaemic agents were uncertain. No studies evaluated treatment on risks of fatigue, life participation, amputation or fracture. AUTHORS' CONCLUSIONS GLP-1 receptor agonists probably reduced all-cause death but may have little or no effect on cardiovascular death in people with CKD and diabetes. GLP-1 receptor agonists probably lower major cardiovascular events, probably have little or no effect on kidney failure and composite kidney outcomes, and may have little or no effect on the risk of severe hypoglycaemia in people with CKD and diabetes.
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Affiliation(s)
- Patrizia Natale
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Department of Precision and Regenerative Medicine and Ionian Area (DIMEPRE-J), University of Bari Aldo Moro, Bari, Italy
| | - Suetonia C Green
- Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand
| | | | - Giovanni Pellegrino
- Department of Precision and Regenerative Medicine and Ionian Area (DIMEPRE-J), University of Bari Aldo Moro, Bari, Italy
| | - Tadashi Toyama
- Department of Nephrology, Kanazawa University, Kanazawa, Japan
- Innovative Clinical Research Center, Kanazawa University, Kanazawa, Japan
| | - Giovanni Fm Strippoli
- Department of Precision and Regenerative Medicine and Ionian Area (DIMEPRE-J), University of Bari Aldo Moro, Bari, Italy
- Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
- Cochrane Kidney and Transplant, Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
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Chen TH, Tseng CJ, Li YR, Lin Y, Chen DY, Yang NI, Wang TH, Hung MJ, Tsai ML. Glucagon-like peptide 1 receptor agonists outperform basal insulin in cardiovascular and renal outcomes for type 2 diabetes mellitus: a retrospective cohort study. Acta Diabetol 2025:10.1007/s00592-024-02443-6. [PMID: 39812791 DOI: 10.1007/s00592-024-02443-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 10/22/2024] [Accepted: 12/29/2024] [Indexed: 01/16/2025]
Abstract
PURPOSE Glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) and basal insulin are currently used in the treatment of type 2 diabetes mellitus (T2DM) as long-acting injectables. In this study, we aimed to compare the cardiovascular (CV) and renal outcomes of GLP-1 RAs and basal insulin treatment in patients with T2DM. METHOD We conducted a propensity score-matched cohort study of patients from Chang Gung Memorial Hospital institutions between 2013 and 2021. A diverse patient base from multiple centers was enrolled to enhance the applicability of the findings, including patients with T2DM who were prescribed either GLP-1 RAs or basal insulin. RESULTS Over a mean follow-up period of 2.2 years, 10,839 patients were collected (mean age = 54.3 years; 54.2% men). Among the propensity score-matched patients, 45 (2.23%) in the GLP-1 RA group (2,854 patients) and 72 (3.56%) in the basal insulin group (7,985 patients) experienced 3-point major adverse cardiovascular events (3P-MACEs; hazard ratio [HR] 0.68, 95% CI 0.47-0.99, P =.44). Additionally, composite renal outcomes were observed in 237 (11.7%) patients in the GLP-1 RA group and 360 (17.8%) in the basal insulin group (HR 0.69, 95% CI 0.59-0.81, P <.001). CONCLUSIONS In patients with T2DM, GLP-1 RAs were associated with more favorable cardiovascular and renal outcomes than basal insulin, suggesting that GLP-1 RA treatment may be a preferable option for managing T2DM with a lower risk of CV and renal complications.
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Affiliation(s)
- Tien-Hsing Chen
- Division of Cardiology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chin-Ju Tseng
- Division of Cardiology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yan-Rong Li
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yuan Lin
- Department of Emergency Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Dong-Yi Chen
- Division of Cardiology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ning-I Yang
- Division of Cardiology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Te-Hsiung Wang
- Department of Emergency Medicine, Tazuke Kofukai, Medical Research Institute, Kitano Hospital, Osaka, Japan
| | - Ming-Jui Hung
- Division of Cardiology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ming-Lung Tsai
- Division of Cardiology, Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, New Taipei, Taiwan.
- College of Medicine, Chang Gung University, Taoyuan, Taiwan.
- College of Management, Chang Gung University, Taoyuan, Taiwan.
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Butalia S, Bajaj HS, Jain R, Leung K, Mansell K, Reichert SM, Senior P, Shah BR. The User's Guide to the Pharmacologic Glycemic Management of Type 2 Diabetes in Adults---2024 Update. Can J Diabetes 2024; 48:425-430. [PMID: 39550177 DOI: 10.1016/j.jcjd.2024.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Indexed: 11/18/2024]
Affiliation(s)
- Sonia Butalia
- Division of Endocrinology and Metabolism, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | | | - Rahul Jain
- Department of Family and Community Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Karen Leung
- Department of Family Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Kerry Mansell
- College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Sonja M Reichert
- Department of Family Medicine, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada
| | - Peter Senior
- Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
| | - Baiju R Shah
- Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
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Malighetti ME, Molteni L, Orsi E, Serra R, Gaglio A, Mazzoleni F, Russo F, Bossi AC. IDegLira improves time in range in a cohort of patients with type 2 diabetes: TiREX study. Acta Diabetol 2024:10.1007/s00592-024-02361-7. [PMID: 39235480 DOI: 10.1007/s00592-024-02361-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 05/07/2024] [Accepted: 07/27/2024] [Indexed: 09/06/2024]
Abstract
AIMS To assess the effects of IDegLira on glucometric indices deriving from intermittently scanned Continuous Glucose Monitoring (isCGM) in patients with type 2 diabetes (T2D). METHODS Retrospective, observational, cohort, multi-center, "pre - post" study. All adults consecutively identified in the medical records who started treatment with IDegLira, and for whom an isCGM report before and after the initiation of IDegLira was available were included in the study. Time in range (TIR) represented the primary endpoint. Additional glucometric indices, insulin doses and body weight were also assessed. RESULTS Overall, 87 patients were included by 5 diabetes centers [mean age 70.2 ± 11.0 years, mean duration of T2D 15.5 ± 9.6 years; BMI 29.4 ± 5.4 kg/m2, baseline HbA1c 9.1 ± 2.1%, 33% insulin naïve, 20.7% treated with basal-oral therapy (BOT), and 46% treated with multiple daily injections of insulin (MDI)]. After an average of 1.7 weeks from IDegLira initiation, TIR significantly increased from 56.8 ± 23.5% to 81.3 ± 13.5% (p < 0.0001), TAR decreased from 42.3 ± 24.2% to 17.1 ± 13.6% (p < 0.0001), while TBR remained steadily low (from 1.3 ± 2.3% to 1.4 ± 2.6%; p = 0.62). Estimated HbA1c decreased from 9.1 ± 2.1% to 6.7 ± 0.6% (p < 0.0001) and percentage of patients with a blood glucose coefficient of variation ≥ 36% dropped from 33.2 to 13.8% (p = 0.0005). In patients on MDI, the reduction in the total insulin dose was substantial (from 55.8 ± 31.2 IU to 27.2 ± 12.3 U). CONCLUSIONS In T2D patients with poor metabolic control, either insulin naïve or treated with BOT or MDI, the introduction of IDegLira produces a significant increase in the time spent in good metabolic control and a marked reduction in glycemic fluctuations.
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Affiliation(s)
| | - Laura Molteni
- Ospedale Sacra Famiglia Fatebenefratelli - via Fatebenefratelli 20, 22036, Erba (CO), Italy
| | - Emanuela Orsi
- Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico - via Francesco Sforza, 28-20122, Milano, Italy
| | - Roberta Serra
- Fondazione Giuseppina Brunenghi - via Beccadello 6, 26012, Castelleone (CR), Italy
| | - Alessia Gaglio
- Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico - via Francesco Sforza, 28-20122, Milano, Italy
| | | | - Filomena Russo
- Casa di Cura Ambrosiana - Piazza Monsignor Moneta 1, 20090, Cesano Boscone (MI), Italy
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5
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Haluzik M, Taybani Z, Araszkiewicz A, Cerghizan A, Mankovsky B, Zuhdi A, Malecki M. Expert Opinion on Optimising Type 2 Diabetes Treatment Using Fixed-Ratio Combination of Basal Insulin and GLP-1 RA for Treatment Intensification and Simplification. Diabetes Ther 2024; 15:1673-1685. [PMID: 38935189 PMCID: PMC11263442 DOI: 10.1007/s13300-024-01610-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 04/18/2024] [Accepted: 06/06/2024] [Indexed: 06/28/2024] Open
Abstract
The management of type 2 diabetes (T2D) often necessitates treatment intensification, and sometimes simplification to achieve glycaemic targets and mitigate complications. This expert opinion paper evaluates the use and positioning of the fixed-ratio combinations (FRCs) of basal insulin (BI) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in optimising T2D management. On the basis of the evidence presented and discussions, these FRCs offer a promising approach for both treatment intensification and simplification in people with suboptimal glucose control despite receiving various therapies. In treatment intensification, FRCs provide a synergistic effect by addressing multiple pathophysiological defects contributing to hyperglycaemia. These FRCs effectively control both fasting and postprandial glucose (PPG) excursions, offering significantly improved glycaemic control with a lower hypoglycaemia risk and weight neutrality compared to traditional or complex insulin regimens. Moreover, the reduced injection frequency (once daily) and flexibility in the dosing schedule (with any major meal of the day) help mitigate patient resistance to insulin initiation or titration. This further reduces treatment burden, facilitating treatment adherence and enhancing patient convenience. These key benefits of FRCs over complex insulin regimens play a crucial role in long-term glycaemic management and overall treatment outcomes. Hence, the timely use of FRCs in the treatment algorithm for people with T2D represents a valuable strategy for optimising glycaemic control, addressing treatment barriers and enhancing patient-reported outcomes.
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Affiliation(s)
- Martin Haluzik
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Vídeňská 1958/9, 140 21, Prague 4, Czech Republic.
| | - Zoltan Taybani
- 1st Department of Endocrinology, Békés County Central Hospital, Dr Réthy Pál Member Hospital, Békécsaba, Hungary
| | - Aleksandra Araszkiewicz
- Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznań, Poland
| | - Anca Cerghizan
- Diabetes Center, Emergency Country Hospital, Cluj-Napoca-Napoca, Romania
| | - Boris Mankovsky
- Department of Diabetology, National Healthcare University of Ukraine, Kiev, Ukraine
| | - Agbaria Zuhdi
- Clalit Health Services, Degani, Hadera, Israel
- Taybeh Specialist Doctor's Clinic, Taybeh, Israel
| | - Maciej Malecki
- Department of Metabolic Diseases, Jagiellonian University Medical College, Kraków, Poland
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Ramírez-Rincón A, Henao-Carrillo D, Omeara M, Oliveros J, Assaf J, Ordóñez JE, Prasad P, Alzate MA. SPIRIT: Assessing Clinical Parameters Associated with Using IDegLira in Patients with Type 2 Diabetes in a Real-World Setting in Colombia. Diabetes Ther 2024; 15:1535-1545. [PMID: 38717577 PMCID: PMC11211291 DOI: 10.1007/s13300-024-01593-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 03/07/2024] [Accepted: 04/17/2024] [Indexed: 06/28/2024] Open
Abstract
INTRODUCTION Insulin degludec/liraglutide (IDegLira) is a fixed-ratio combination of insulin degludec (a basal insulin) and liraglutide (a glucagon-like peptide-1 receptor agonist [GLP-1RA]). This study aimed to investigate clinical outcomes in people with type 2 diabetes mellitus (T2DM) after initiating IDegLira treatment in a real-world setting in Colombia. METHODS SPIRIT is a non-interventional, single-arm, retrospective chart review study to assess clinical outcomes in people with T2DM. Participating patients were switched from a treatment regimen of basal insulin (with or without oral antidiabetics [OADs]) and started on treatment with IDegLira a minimum of 26 ± 6 weeks before the data collection start date. Data were collected from the medical records of 175 patients in ten clinical centers across Colombia. RESULTS Compared with baseline, there was a significant reduction in glycated hemoglobin (HbA1c) (1.3%; 95% confidence interval [CI] - 1.6 to - 1.0; p < 0.0001) after 26 ± 6 weeks of follow-up. The mean HbA1c at baseline and at the end of the study was 9.1% and 7.8%, respectively. In addition, IDegLira significantly reduced absolute body weight by 1 kg (95% CI - 1.5 to - 0.5; p < 0.0001), from a mean of 76.1 kg at baseline to 75.1 kg after follow-up. The mean IDegLira dose at the end of the study was 21.3 U, and no severe hypoglycemic events were observed during the follow-up period. CONCLUSION In real-world practice, initiating IDegLira in patients with T2DM previously treated with basal insulin (± OAD) was associated with improved glycemic control, reduced body weight and reduced risk of hypoglycemia. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT05324462.
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Affiliation(s)
| | | | | | - Julio Oliveros
- Universidad Autónoma de Bucaramanga, Bucaramanga, Colombia
| | - José Assaf
- Universidad Autónoma de Bucaramanga, Bucaramanga, Colombia
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Moon JS, Kang S, Choi JH, Lee KA, Moon JH, Chon S, Kim DJ, Kim HJ, Seo JA, Kim MK, Lim JH, Song YJ, Yang YS, Kim JH, Lee YB, Noh J, Hur KY, Park JS, Rhee SY, Kim HJ, Kim HM, Ko JH, Kim NH, Kim CH, Ahn J, Oh TJ, Kim SK, Kim J, Han E, Jin SM, Bae J, Jeon E, Kim JM, Kang SM, Park JH, Yun JS, Cha BS, Moon MK, Lee BW. 2023 Clinical Practice Guidelines for Diabetes Management in Korea: Full Version Recommendation of the Korean Diabetes Association. Diabetes Metab J 2024; 48:546-708. [PMID: 39091005 PMCID: PMC11307112 DOI: 10.4093/dmj.2024.0249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 05/17/2024] [Accepted: 06/20/2024] [Indexed: 08/04/2024] Open
Affiliation(s)
- Jun Sung Moon
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Shinae Kang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jong Han Choi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
| | - Kyung Ae Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
| | - Joon Ho Moon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Suk Chon
- Department of Endocrinology and Metabolism, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Dae Jung Kim
- Department of Endocrinology and Metabolism, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea
| | - Hyun Jin Kim
- Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, Korea
| | - Ji A Seo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Mee Kyoung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jeong Hyun Lim
- Department of Food Service and Nutrition Care, Seoul National University Hospital, Seoul, Korea
| | - Yoon Ju Song
- Department of Food Science and Nutrition, The Catholic University of Korea, Bucheon, Korea
| | - Ye Seul Yang
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Hyeon Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - You-Bin Lee
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Junghyun Noh
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
| | - Kyu Yeon Hur
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jong Suk Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Youl Rhee
- Department of Endocrinology and Metabolism, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Hae Jin Kim
- Department of Endocrinology and Metabolism, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea
| | - Hyun Min Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Jung Hae Ko
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Nam Hoon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Chong Hwa Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea
| | - Jeeyun Ahn
- Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Tae Jung Oh
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Soo-Kyung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Jaehyun Kim
- Department of Pediatrics, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Eugene Han
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Sang-Man Jin
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jaehyun Bae
- Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Korea
| | - Eonju Jeon
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Ji Min Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea
| | - Seon Mee Kang
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Korea
| | - Jung Hwan Park
- Division of Endocrinology & Metabolism, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Jae-Seung Yun
- Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Bong-Soo Cha
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Min Kyong Moon
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Byung-Wan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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Di Loreto C, Celleno R, Pezzuto D, Ambrosi F, Bellavita S, Biagini M, Passeri M, Del Sindaco P. Effectiveness, Simplification and Persistence of IDegLira in Poorly Controlled People with Type 2 Diabetes: A 4-Year Follow-Up Real-World Study. Diabetes Ther 2024; 15:1313-1331. [PMID: 38605275 PMCID: PMC11096145 DOI: 10.1007/s13300-024-01564-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 02/09/2024] [Accepted: 03/11/2024] [Indexed: 04/13/2024] Open
Abstract
INTRODUCTION Efficacy and safety of the fixed ratio combination of insulin degludec and liraglutide (IDegLira) has been largely documented. However, long-term data are limited. This study aimed at describing persistence in therapy and the effectiveness at 48 months of IDegLira. METHODS We conducted an observational study based on retrospective chart review. All patients treated with IDegLira during 2018-2022 were included. Data on treatment approaches and clinical outcomes were collected at the first prescription of IDegLira (T0) and after 6, 12, 24, 36, and 48 months. RESULTS Overall, 156 patients (mean age 68 years, 64.1% men) started IDegLira, of whom 88 (56.4%) were previously treated with basal-oral therapy (BOT) and 68 (43.6%) with basal-bolus schemes (BB). Before starting IDegLira, 23.8% were treated with ≥ 2 oral antihyperglycemic agents in association with insulin; at T0, the proportion decreased to 3.2%. Short-acting insulin was discontinued after the first week. After 48 months, levels of HbA1c were significantly reduced by 1.34% in the BOT group and 1.07% in the BB group (p < 0.0001 in both groups). In the BOT group, FBG levels decreased by about 50 mg/dl and body weight was unchanged. In the BB group, FBG levels decreased by about 40 mg/dl and body weight was significantly reduced by an average of 7.7 kg. Five patients (3.2%) interrupted therapy with IDegLira during 48 months, and no severe hypoglycemia occurred. CONCLUSIONS Our study emphasizes the important role of IDegLira in maintaining a good metabolic control while minimizing the risk of major hypoglycemia and weight gain in the long term. The substantial simplification of treatment schemes can increase adherence.
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Affiliation(s)
- Chiara Di Loreto
- U.O.S. Diabetologia, Distretto del Perugino, USL Umbria 1, "Poliambulatorio Europa", Perugia, Italy.
| | - Roberta Celleno
- U.O.S. Diabetologia, Distretto del Perugino, USL Umbria 1, "Poliambulatorio Europa", Perugia, Italy
| | - Debora Pezzuto
- U.O.S. Diabetologia, Distretto del Perugino, USL Umbria 1, "Poliambulatorio Europa", Perugia, Italy
| | - Franca Ambrosi
- U.O.S. Diabetologia, Distretto del Perugino, USL Umbria 1, "Poliambulatorio Europa", Perugia, Italy
| | - Silvia Bellavita
- U.O.S. Diabetologia, Distretto del Perugino, USL Umbria 1, "Poliambulatorio Europa", Perugia, Italy
| | - Marinella Biagini
- U.O.S. Diabetologia, Distretto del Perugino, USL Umbria 1, "Poliambulatorio Europa", Perugia, Italy
| | - Monica Passeri
- U.O.S. Diabetologia, Distretto del Perugino, USL Umbria 1, "Poliambulatorio Europa", Perugia, Italy
| | - Paola Del Sindaco
- U.O.S. Diabetologia, Distretto del Perugino, USL Umbria 1, "Poliambulatorio Europa", Perugia, Italy
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9
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McGill JB, Hirsch IB, Parkin CG, Aleppo G, Levy CJ, Gavin JR. The Current and Future Role of Insulin Therapy in the Management of Type 2 Diabetes: A Narrative Review. Diabetes Ther 2024; 15:1085-1098. [PMID: 38573469 PMCID: PMC11043311 DOI: 10.1007/s13300-024-01569-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 02/28/2024] [Accepted: 03/14/2024] [Indexed: 04/05/2024] Open
Abstract
Early initiation of intensive insulin therapy has been demonstrated to be effective in controlling glycemia and possibly preserving beta-cell function. Innovations in insulin formulations and delivery systems continue. However, we have seen an acceleration in the development of new classes of diabetes medications for individuals with type 2 diabetes and obesity, such as, for example, glucagon-like peptide-1 receptor agonists (GLP-1 RAs). These formulations have been shown to confer significant benefits in achieving good glycemic control with reduced hypoglycemia risk, weight loss, and cardiorenal protection. Therefore, it is reasonable to question whether there is still a role for insulin therapy in the management of type 2 diabetes. However, there are clear limitations inherent to GLP-1 RA therapy, including high rates of suboptimal adherence and treatment discontinuation due to high cost and side effects, which diminish long-term efficacy, and supply issues. In addition, newer formulations have shown improvements in convenience and tolerability, and have been shown to be even more effective when used in conjunction with basal insulin. In this narrative review, we discuss current evidence that supports GLP-1 RA use in combination with insulin therapy and the potential pitfalls of reliance on GLP-1 RAs as a substitute for insulin therapy.
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Affiliation(s)
- Janet B McGill
- Division of Endocrinology, Metabolism and Lipid Research, School of Medicine, Washington University in St. Louis, 660 S. Euclid, Campus Box 8127, St. Louis, MO, 63110, USA
| | - Irl B Hirsch
- UW Medicine Diabetes Institute, University of Washington School of Medicine, 750 Republican Street, Building F, Seattle, WA, 98109, USA
| | - Christopher G Parkin
- CGParkin Communications, Inc., 2675 Windmill Pkwy, Ste. 2721, Henderson, NV, 89074, USA.
| | - Grazia Aleppo
- Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine Northwestern University, 675 N St Clair St Galter Pavilion, Ste 14-100, Chicago, IL, 60611, USA
| | - Carol J Levy
- Division of Endocrinology, Diabetes, and Metabolism, Mount Sinai Diabetes Center and T1D Clinical Research, Icahn School of Medicine at Mount Sinai, 5 E 98th St, New York, NY, 10029, USA
| | - James R Gavin
- Emory University School of Medicine, 100 Woodruff Circle, Atlanta, GA, 30322, USA
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10
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Philis-Tsimikas A, Aroda VR, De Block C, Billings LK, Liebl A, Sivarathinasami R, D’Cruz JM, Lingvay I. Higher Derived Time in Range With IDegLira Versus Insulin Glargine U100 in People With Type 2 Diabetes. J Diabetes Sci Technol 2024; 18:653-659. [PMID: 36710452 PMCID: PMC11089877 DOI: 10.1177/19322968221149041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Derived time in range (dTIR), calculated from self-monitored blood glucose (SMBG-dTIR) profiles, has demonstrated correlation with risk of cardiovascular and microvascular complications. This post hoc analysis of the DUAL V and DUAL VIII trials aimed to compare dTIR with an insulin degludec/liraglutide fixed-ratio combination (IDegLira) versus insulin glargine 100 units/mL (glargine U100) in people with type 2 diabetes (T2D). MATERIALS AND METHODS Nine-point SMBG profiles were taken more than 24 hours at baseline and end of trial (EOT: 26 weeks [DUAL V] and 104 weeks [DUAL VIII]) and used to derive the percentage of readings within target range (70-180 mg/dL). Estimated treatment differences (ETDs, IDegLira-glargine U100) were analyzed using analysis of covariance, with treatment as fixed effects and baseline response as a covariate. RESULTS ETDs for change from baseline to EOT in dTIR were significantly greater with IDegLira versus glargine U100 in DUAL V (4.18%, P = .027) and DUAL VIII (5.17%, P = .001). The proportions of people achieving ≥70% dTIR at EOT with IDegLira and glargine U100, respectively, were 62% and 60% in DUAL V (P = .7541), and 50% and 26% in DUAL VIII (P < .0001). The proportion achieving a ≥5% increase in dTIR from baseline to EOT with IDegLira and glargine U100 was 63% in both groups in DUAL V (P = .9043), and 44% and 25%, respectively, in DUAL VIII (P < .0001). CONCLUSIONS IDegLira was associated with significantly greater increases in dTIR versus basal insulin alone in people with T2D. TRIAL ID(S) ClinicalTrials.gov, NCT01952145 (DUAL V); ClinicalTrials.gov, NCT02501161 (DUAL VIII).
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Affiliation(s)
| | - Vanita R. Aroda
- Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Christophe De Block
- Department of Endocrinology-Diabetology-Metabolism, Antwerp University Hospital, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
| | - Liana K. Billings
- NorthShore University HealthSystem/University of Chicago Pritzker School of Medicine, Skokie, IL, USA
| | - Andreas Liebl
- Center for Diabetes and Metabolism, m&i-Fachklinik, Bad Heilbrunn, Bad Heilbrunn, Germany
| | | | - John M. D’Cruz
- Novo Nordisk Service Centre India Private Ltd, Bangalore, India
| | - Ildiko Lingvay
- The University of Texas Southwestern Medical Center, Dallas, TX, USA
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11
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Fadini GP, Buzzetti R, Pitocco D, Tortato E, Scatena A, Lamacchia O, Lastoria G, Simoni L, Consoli A. IDegLira for the real-world treatment of type 2 diabetes in Italy. Final results from the REX observational study. Diabetes Obes Metab 2024; 26:1746-1756. [PMID: 38327240 DOI: 10.1111/dom.15486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 11/30/2023] [Revised: 01/15/2024] [Accepted: 01/21/2024] [Indexed: 02/09/2024]
Abstract
AIM The study was designed to generate real-world evidence on IDegLira in the Italian clinical practice in two groups of patients with type 2 diabetes (T2D), switching to IDegLira either from a basal only (basal group) or basal-bolus insulin regimen (BB group). MATERIALS AND METHODS This was a non-interventional, multicentre, single-cohort, prospective study assessing the long-term glycaemic control in patients with T2D, who switched to IDegLira from a basal insulin ± glucose-lowering medication regimen with or without a bolus insulin component for approximately 18 months, conducted in 28 Italian diabetes centres. The primary endpoint was the change in glycated haemoglobin (HbA1c) levels from baseline to 6 months after IDegLira initiation. RESULTS The study included 358 patients with a mean age 67.2 years and diabetes duration of 15.7 years. HbA1c significantly decreased from IDegLira start to all study time points in the overall population (basal group -1.19%; BB group -0.60% at the end of observation). Patients achieving HbA1c <7% levels increased from 12.9% (n = 43) to 40.3% (n = 110) at 18 months. Fasting blood glucose and body weight also significantly decreased in both groups, although more in the BB group. Overall, 14.3% of completed patients had an intensification of treatment (mainly in the basal group) and 48.6% had a simplification of treatment (mainly in the BB group). CONCLUSIONS Switching to IDegLira in a real-world clinical setting is a valid therapeutic option for patients with T2D with inadequate glycaemic control on basal or BB insulin regimen and/or need to simplify their insulin therapy, with specific reasons and therapeutic goals according to different T2D management trajectories.
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Affiliation(s)
- Gian Paolo Fadini
- Department of Medicine, University of Padova, Padua, Italy
- Division of Metabolic Diseases, Padova Hospital, Padua, Italy
| | - Raffaella Buzzetti
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Dario Pitocco
- Diabetology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Elena Tortato
- Metabolic Diseases and Diabetology Department, IRCCS INRCA, Ancona, Italy
| | | | - Olga Lamacchia
- Endocrinology Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Giusi Lastoria
- Clinical Medical & Regulatory Department, Novo Nordisk SpA, Rome, Italy
| | - Lucia Simoni
- Medineos Observational Research, an IQVIA Company, Modena, Italy
| | - Agostino Consoli
- Department of Medicine and Aging Sciences (DMSI) and Center for Advanced Studies and Technology (CAST), University G. D'Annunzio, Chieti, Italy
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12
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Ahmed R, de Souza RJ, Li V, Banfield L, Anand SS. Twenty years of participation of racialised groups in type 2 diabetes randomised clinical trials: a meta-epidemiological review. Diabetologia 2024; 67:443-458. [PMID: 38177564 PMCID: PMC10844363 DOI: 10.1007/s00125-023-06052-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 07/27/2023] [Accepted: 10/16/2023] [Indexed: 01/06/2024]
Abstract
AIMS/HYPOTHESIS Type 2 diabetes mellitus prevalence is increasing globally and the greatest burden is borne by racialised people. However, there are concerns that the enrolment of racialised people into RCTs is limited, resulting in a lack of ethnic and racial diversity. This may differ depending whether an RCT is government funded or industry funded. The aim of this study was to review the proportions of racialised and white participants included in large RCTs of type 2 diabetes pharmacotherapies relative to the disease burden of type 2 diabetes in these groups. METHODS The Ovid MEDLINE database was searched from 1 January 2000 to 31 December 2020. English language reports of RCTs of type 2 diabetes pharmacotherapies published in select medical journals were included. Studies were included in this review if they had a sample size of at least 100 participants and all participants were adults with type 2 diabetes. Industry-funded trials must have recruited participants from at least two countries. Government-funded trials were not held to the same standard because they are typically conducted in a single country. Data including the numbers and proportions of participants by ethnicity and race were extracted from trial reports. The participation-to-prevalence ratio (PPR) was calculated for each trial by dividing the percentage of white and racialised participants in each trial by the percentage of white and racialised participants with type 2 diabetes, respectively, for the regions of recruitment. A random-effects meta-analysis was used to generate the pooled PPRs and 95% CIs across study types. A PPR <0.80 indicates under-representation and a PPR >1.20 indicates over-representation. Risk of bias assessments were not conducted for this study as the objective was to examine recruitment of racialised and white participants rather than evaluate the trustworthiness of clinical trial outcomes. RESULTS A total of 83 trials were included, involving 283,122 participants, of which 15 were government-funded and 68 were industry-funded trials. In government-funded trials, the PPR for white participants was 1.11 (95% CI 0.99, 1.24) and the PPR for racialised participants was 0.72 (95% CI 0.60, 0.86). In industry-funded trials, the PPR for white participants was 1.95 (95% CI 1.74, 2.18) and the PPR for racialised participants was 0.36 (95% CI 0.32, 0.42). The limitations of this study include the reliance on investigator-reported ethnicity and race to classify participants as 'white' or 'racialised', the use of estimates for type 2 diabetes prevalence and demographic data, and the high levels of heterogeneity of pooled estimates. However, despite these limitations, the results were consistent with respect to direction. CONCLUSIONS/INTERPRETATION Racialised participants are under-represented in government- and industry-funded type 2 diabetes trials. Strategies to improve recruitment and enrolment of racialised participants into RCTs should be developed. REGISTRATION Open Science Framework registration no. f59mk ( https://osf.io/f59mk ) FUNDING: The authors received no financial support for this research or authorship of the article.
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Affiliation(s)
- Rabeeyah Ahmed
- Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
- Chanchlani Research Centre, McMaster University, Hamilton, ON, Canada
| | - Russell J de Souza
- Chanchlani Research Centre, McMaster University, Hamilton, ON, Canada
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada
| | - Vincent Li
- Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
| | - Laura Banfield
- Health Sciences Library, McMaster University, Hamilton, ON, Canada
| | - Sonia S Anand
- Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
- Chanchlani Research Centre, McMaster University, Hamilton, ON, Canada.
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.
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13
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Liu Y, Li X, Zheng Y, Wang X, Wang X. IDegLira for type 2 diabetes: a systematic review and meta-analysis. Endocrine 2024; 83:648-658. [PMID: 37768513 DOI: 10.1007/s12020-023-03543-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 06/19/2023] [Accepted: 09/18/2023] [Indexed: 09/29/2023]
Abstract
OBJECTIVES IDegLira is a novel fixed-ratio soluble combination of insulin degludec and the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide approved for type 2 diabetes (T2D) patients. Individual trials have assessed the clinical profile of IDegLira vs different comparators. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of IDegLira for T2D. METHODS PubMed, Embase, Cochrane Library and ClinicalTrials.gov were searched from inception to August 15, 2023. The primary outcomes included change from baseline in haemoglobin A1c (HbA1c) and body weight. Risk ratios (RR), mean differences (MD), and 95% confidence intervals (CI) were calculated to evaluate the outcomes. RESULTS This meta-analysis identified 1044 citations, and included 13 eligible trials, enroling 7773 patients. Compared with the control groups, IDegLira was optimal in change in HbA1c, percentage of patients achieving HbA1c < 7%, percentage of patients achieving HbA1c < 6.5%, HbA1c < 7.0% without weight gain and without severe or blood glucose (BG)-confirmed hypoglycaemia episodes, HbA1c < 6.5% without weight gain and without severe or BG-confirmed hypoglycaemia episodes, change in fasting plasma glucose, change in self-measured plasma glucose, change in systolic pressure, and total daily insulin dose. No difference was found between the IDegLira and control groups in terms of change in body weight, change in diastolic pressure, severe or BG-confirmed symptomatic hypoglycaemia, nocturnal severe or BG-confirmed symptomatic hypoglycaemia, adverse events or serious adverse events. CONCLUSIONS In patients with T2D, IDegLira improved glycaemic control whilst balancing out risk for hypoglycaemia and gastrointestinal side effects.
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Affiliation(s)
- Yang Liu
- Department of Pharmacy, Hebei Medical University Third Hospital, Shijiazhuang, China
| | - Xuejing Li
- Department of Pharmacy, Hebei Medical University Third Hospital, Shijiazhuang, China
| | - Yingying Zheng
- Department of Pharmacy, Hebei Medical University Third Hospital, Shijiazhuang, China
| | - Xiaoli Wang
- Department of Pharmacy, Hebei Medical University Third Hospital, Shijiazhuang, China
| | - Xianying Wang
- Department of Pharmacy, Hebei Medical University Third Hospital, Shijiazhuang, China.
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14
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Wang R, Luo S, Xiao Z, Zhou Z. Efficacy and safety of fixed-ratio combination insulin degludec/liraglutide in type 2 diabetes: A systematic review and meta-analysis of randomised controlled trials. Diabetes Metab Res Rev 2024; 40:e3752. [PMID: 38013215 DOI: 10.1002/dmrr.3752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 06/02/2023] [Revised: 09/30/2023] [Accepted: 11/05/2023] [Indexed: 11/29/2023]
Abstract
BACKGROUND The efficacy and safety of fixed-ratio combination insulin degludec/liraglutide (IDegLira) for type 2 diabetes (T2DM) were extensively investigated by the global DUAL trials. However, the evidence on its efficacy and safety in T2DM has not been systematically reviewed. METHODS Randomized controlled trials published in English that compared IDegLira with placebo or GLP-1 agonists or insulin in patients with T2DM were selected up to December 2022. Data on the study characteristics, efficacy and safety outcomes were extracted. We compared the efficacy and safety between "IDegLira versus Insulin," "IDegLira versus GLP-1RA," and "IDegLira versus Placebo". The risk of potential bias was assessed. RESULTS In terms of glycaemic efficacy, IDegLira reduced levels of glycated haemoglobin (HbA1c; weighted mean differences (WMDs) 0.52%, 95% CI 0.33%-0.71%); fasting blood glucose (0.32 mg/dL, 0.14-0.50 mg/dL), and the nine-point self-measured plasma glucose (0.25 mmol/L, 0.25-0.36 mmol/L). Furthermore, IDegLira was generally better in the attainment of HbA1c < 7.0% or ≤6.5%, HbA1c < 7.0% or ≤6.5% without weight gain and/or without severe or blood glucose-confirmed hypoglycaemic episodes. In non-glycaemic efficacy aspects, IDegLira decreased systolic blood pressure but elevated heart rate. In terms of safety outcomes, IDegLira did not appear to be associated with a risk of hypoglycaemia (RR 1.23, 0.85-1.78) and nocturnal hypoglycaemia (0.89, 0.52-1.52) occurring when compared with other hypoglycaemic agents or placebo. CONCLUSIONS IDegLira improves better glycaemic and non-glycaemic outcomes without weight gain and/or without severe or blood glucose-confirmed hypoglycaemic episodes in T2DM. Side effects of IDegLira are mild.
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Affiliation(s)
- Rui Wang
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Shuoming Luo
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Zilin Xiao
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Zhiguang Zhou
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
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15
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Куркин ДВ, Бакулин ДА, Морковин ЕИ, Стрыгин АВ, Горбунова ЮВ, Волотова ЕВ, Робертус АИ, Макаренко ИЕ, Сапарова ВБ, Драй РВ, Петров ВИ. [Fixed ratio combinations GLP-1RA and basal insulin: literature review]. PROBLEMY ENDOKRINOLOGII 2024; 70:91-99. [PMID: 38433545 PMCID: PMC10926250 DOI: 10.14341/probl13312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Academic Contribution Register] [Received: 05/25/2023] [Revised: 07/06/2023] [Accepted: 08/10/2023] [Indexed: 03/05/2024]
Abstract
The progressive nature of type 2 diabetes mellitus leads to the need for insulin therapy in a significant proportion of patients. Very often start of insulin therapy in type 2 diabetes mellitus (T2DM) is associated with weight gain and a significant increase of hypoglycemia's risk. However, innovative options, such as fixed ratio combinations of glucagon-like peptide 1 receptor agonists (GLP-1RA) and basal insulin, minimize weight gain and hypoglycemia risks and allow a greater proportion of patients to achieve individual glycemic control goals without compromising safety parameters. This review includes a description of the randomized clinical trials, as well as the results of real clinical practice of the use of two currently existing fixed ration combinations of GLP-1RA and basal insulin - iDegLira and iGlarLixi.
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Affiliation(s)
- Д. В. Куркин
- Российский университет медицины; Волгоградский государственный медицинский университет
| | | | | | - А. В. Стрыгин
- Волгоградский государственный медицинский университет
| | | | | | | | | | | | | | - В. И. Петров
- Волгоградский государственный медицинский университет
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16
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Terenzi DC, Bakbak E, Teoh H, Krishnaraj A, Puar P, Rotstein OD, Cosentino F, Goldenberg RM, Verma S, Hess DA. Restoration of blood vessel regeneration in the era of combination SGLT2i and GLP-1RA therapy for diabetes and obesity. Cardiovasc Res 2024; 119:2858-2874. [PMID: 38367275 DOI: 10.1093/cvr/cvae016] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 07/12/2022] [Revised: 12/20/2022] [Accepted: 01/05/2023] [Indexed: 02/19/2024] Open
Abstract
Ischaemic cardiovascular diseases, including peripheral and coronary artery disease, myocardial infarction, and stroke, remain major comorbidities for individuals with type 2 diabetes (T2D) and obesity. During cardiometabolic chronic disease (CMCD), hyperglycaemia and excess adiposity elevate oxidative stress and promote endothelial damage, alongside an imbalance in circulating pro-vascular progenitor cells that mediate vascular repair. Individuals with CMCD demonstrate pro-vascular 'regenerative cell exhaustion' (RCE) characterized by excess pro-inflammatory granulocyte precursor mobilization into the circulation, monocyte polarization towards pro-inflammatory vs. anti-inflammatory phenotype, and decreased pro-vascular progenitor cell content, impairing the capacity for vessel repair. Remarkably, targeted treatment with the sodium-glucose cotransporter-2 inhibitor (SGLT2i) empagliflozin in subjects with T2D and coronary artery disease, and gastric bypass surgery in subjects with severe obesity, has been shown to partially reverse these RCE phenotypes. SGLT2is and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have reshaped the management of individuals with T2D and comorbid obesity. In addition to glucose-lowering action, both drug classes have been shown to induce weight loss and reduce mortality and adverse cardiovascular outcomes in landmark clinical trials. Furthermore, both drug families also act to reduce systemic oxidative stress through altered activity of overlapping oxidase and antioxidant pathways, providing a putative mechanism to augment circulating pro-vascular progenitor cell content. As SGLT2i and GLP-1RA combination therapies are emerging as a novel therapeutic opportunity for individuals with poorly controlled hyperglycaemia, potential additive effects in the reduction of oxidative stress may also enhance vascular repair and further reduce the ischaemic cardiovascular comorbidities associated with T2D and obesity.
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Affiliation(s)
- Daniella C Terenzi
- UCD School of Medicine, University College Dublin, Belfield, Dublin 4 D04 V1W8, Ireland
- Division of Cardiovascular Surgery, St. Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada
| | - Ehab Bakbak
- Division of Cardiovascular Surgery, St. Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada
- Department of Pharmacology and Toxicology, University of Toronto, 27 King's College Circle, Toronto, ON M5S 3J3, Canada
| | - Hwee Teoh
- Division of Cardiovascular Surgery, St. Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada
- Division of Endocrinology and Metabolism, St. Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada
| | - Aishwarya Krishnaraj
- Division of Cardiovascular Surgery, St. Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada
- Department of Pharmacology and Toxicology, University of Toronto, 27 King's College Circle, Toronto, ON M5S 3J3, Canada
| | - Pankaj Puar
- Division of Cardiovascular Surgery, St. Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada
| | - Ori D Rotstein
- Division of General Surgery, St. Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada
- Department of Surgery, University of Toronto, Stewart Building, 149 College Street, 5th floor, Toronto, ON M5T 1P5, Canada
| | - Francesco Cosentino
- Cardiology Unit, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Solnavagen 1, 171 77 Solna, Sweden
| | | | - Subodh Verma
- Division of Cardiovascular Surgery, St. Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada
- Department of Pharmacology and Toxicology, University of Toronto, 27 King's College Circle, Toronto, ON M5S 3J3, Canada
- Department of Surgery, University of Toronto, Stewart Building, 149 College Street, 5th floor, Toronto, ON M5T 1P5, Canada
| | - David A Hess
- Department of Pharmacology and Toxicology, University of Toronto, 27 King's College Circle, Toronto, ON M5S 3J3, Canada
- Molecular Medicine Research Laboratories, Krembil Centre for Stem Cells Biology, Robarts Research Institute, University of Western Ontario, 1151 Richmond Street North, London, ON N6H 0E8, Canada
- Department of Physiology and Pharmacology, University of Western Ontario, 1151 Richmond Street North, London, ON N6H 0E8, Canada
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Garnica-Cuellar JC, Morales-Villegas E, López-Forero CA, Monroy-Cruz B, Pariti B, Deshwal S, Sekharan M, Osorio-Hernández M, García-Appendini IC. A Relative Cost of Control Analysis of IDegLira versus Other Forms of Basal Insulin Intensification in Mexico. PHARMACOECONOMICS - OPEN 2023; 7:841-849. [PMID: 37452964 PMCID: PMC10471528 DOI: 10.1007/s41669-023-00421-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Academic Contribution Register] [Accepted: 04/03/2023] [Indexed: 07/18/2023]
Abstract
OBJECTIVES Achieving glycemic control in patients with type 2 diabetes is important as it reduces the risk of complications and their related clinical and economic burden. Yet therapeutic inertia due to the fear of hypoglycemia, complex treatment regimens, weight gain, and therapy costs, among others, limits achieving glycemic control. This analysis aims to assess the short-term cost of control (cost per patient achieving treatment goals) with insulin degludec/liraglutide (IDegLira) versus other forms of basal insulin intensification (insulin glargine titration, basal-bolus therapy, and the combination of insulin glargine and lixisenatide: IGlarLixi) in type 2 diabetes patients not controlled with basal insulin in the Mexican private setting. METHODS The proportion of patients achieving treatment goals was obtained from DUAL V and DUAL VII studies (full trial population) and a indirect treatment comparison analyzing IDegLira versus IGlarLixi. Annual cost of treatment was estimated using unitary costs from IQVIA's Pharmaceutical Market Mexico (PMM) audit and wholesale acquisition costs (both from December 2021). The cost of control was estimated by dividing the annual cost of treatment by the proportion of patients achieving the corresponding treatment goal: glycated hemoglobin (HbA1C) < 7.0%, HbA1C < 7.0% without weight gain, HbA1C < 7.0% without hypoglycemia, and HbA1C < 7.0% without hypoglycemia and weight gain. One-way sensitivity analyses were conducted to assess how variations in the model inputs impacted cost-effectiveness outcomes. RESULTS The proportion of patients achieving treatment goals was higher for IDegLira versus other forms of basal insulin intensification in all endpoints assessed. The annual cost of treatment with IDegLira was similar to the cost of treatment versus IGlarLixi or versus basal-bolus therapy ($54,659 versus $55,831 MXN and $51,008 versus $52,987 MXN, respectively), and higher in comparison with insulin glargine titration ($52,186 versus $40,194 MXN). The cost of controlling one patient with IDegLira was lower than any other form of basal insulin intensification, for all treatment goals. CONCLUSION When integrating the greater clinical efficacy of IDegLira with its annual cost, it can be shown that within 1 year, IDegLira is the best option in terms of value for money for payers in a private healthcare setting in Mexico in comparison with other forms of basal insulin intensification. Thus, investing in IDegLira not only represents a greater clinical benefit, but also an economical one for payers.
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Galindo RJ, Moazzami B, Scioscia MF, Zambrano C, Albury BS, Saling J, Vellanki P, Pasquel FJ, Davis GM, Fayfman M, Peng L, Umpierrez GE. A Randomized Controlled Trial Comparing the Efficacy and Safety of IDegLira Versus Basal-Bolus in Patients With Poorly Controlled Type 2 Diabetes and Very High HbA1c ≥9-15%: DUAL HIGH Trial. Diabetes Care 2023; 46:1640-1645. [PMID: 37459574 PMCID: PMC10465828 DOI: 10.2337/dc22-2426] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 12/13/2022] [Accepted: 06/05/2023] [Indexed: 07/21/2023]
Abstract
OBJECTIVE In participants with type 2 diabetes (T2D) and HbA1c >9.0-10.0%, guidelines recommend treatment with basal-bolus insulin. RESEARCH DESIGN AND METHODS This randomized trial compared the efficacy and safety of insulin degludec and liraglutide (IDegLira) and basal-bolus among participants with high HbA1c ≥9.0-15.0%, previously treated with 2 or 3 oral agents and/or basal insulin, allocated (1:1) to basal-bolus (n = 73) or IDegLira (n = 72). The primary end point was noninferiority (0.4%) in HbA1c reduction between groups. RESULTS Among 145 participants (HbA1c 10.8% ± 1.3), there was no statistically significant difference in HbA1c reduction (3.18% ± 2.29 vs. 3.00% ± 1.79, P = 0.65; estimated treatment difference (ETD) 0.18%, 95% CI -0.59, 0.94) between the IDegLira and basal-bolus groups. IDegLira resulted in significantly lower rates of hypoglycemia <70 mg/dL (26% vs. 48%, P = 0.008; odds ratio 0.39, 95% CI 0.19, 0.78), and less weight gain (1.24 ± 8.33 vs. 5.84 ± 6.18 kg, P = 0.001; ETD -4.60, 95% CI -7.33, -1.87). CONCLUSIONS In participants with T2D and HbA1c ≥9.0-15.0%, IDegLira resulted in similar HbA1c reduction, less hypoglycemia, and less weight gain compared with the basal-bolus regimen.
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Affiliation(s)
- Rodolfo J. Galindo
- Division of Endocrinology, Department of Medicine, Emory University School of Medicine, Atlanta, GA
| | - Bobak Moazzami
- Division of Endocrinology, Department of Medicine, Emory University School of Medicine, Atlanta, GA
| | - Maria F. Scioscia
- Division of Endocrinology, Department of Medicine, Emory University School of Medicine, Atlanta, GA
| | - Cesar Zambrano
- Division of Endocrinology, Department of Medicine, Emory University School of Medicine, Atlanta, GA
| | - Bonnie S. Albury
- Division of Endocrinology, Department of Medicine, Emory University School of Medicine, Atlanta, GA
| | - Jarrod Saling
- Division of Endocrinology, Department of Medicine, Emory University School of Medicine, Atlanta, GA
| | - Priyathama Vellanki
- Division of Endocrinology, Department of Medicine, Emory University School of Medicine, Atlanta, GA
| | - Francisco J. Pasquel
- Division of Endocrinology, Department of Medicine, Emory University School of Medicine, Atlanta, GA
| | - Georgia M. Davis
- Division of Endocrinology, Department of Medicine, Emory University School of Medicine, Atlanta, GA
| | - Maya Fayfman
- Division of Endocrinology, Department of Medicine, Emory University School of Medicine, Atlanta, GA
| | - Limin Peng
- Deartment of Biostatistics, Rollins School of Public Health, Emory University, Atlanta, GA
| | - Guillermo E. Umpierrez
- Division of Endocrinology, Department of Medicine, Emory University School of Medicine, Atlanta, GA
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Choi JH, Lee KA, Moon JH, Chon S, Kim DJ, Kim HJ, Kim NH, Seo JA, Kim MK, Lim JH, Song Y, Yang YS, Kim JH, Lee YB, Noh J, Hur KY, Park JS, Rhee SY, Kim HJ, Kim HM, Ko JH, Kim NH, Kim CH, Ahn J, Oh TJ, Kim SK, Kim J, Han E, Jin SM, Choi WS, Moon MK. 2023 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association. Diabetes Metab J 2023; 47:575-594. [PMID: 37793979 PMCID: PMC10555541 DOI: 10.4093/dmj.2023.0282] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 08/20/2023] [Accepted: 09/14/2023] [Indexed: 10/06/2023] Open
Abstract
In May 2023, the Committee of Clinical Practice Guidelines of the Korean Diabetes Association published the revised clinical practice guidelines for Korean adults with diabetes and prediabetes. We incorporated the latest clinical research findings through a comprehensive systematic literature review and applied them in a manner suitable for the Korean population. These guidelines are designed for all healthcare providers nationwide, including physicians, diabetes experts, and certified diabetes educators who manage patients with diabetes or individuals at risk of developing diabetes. Based on recent changes in international guidelines and the results of a Korean epidemiological study, the recommended age for diabetes screening has been lowered. In collaboration with the relevant Korean medical societies, recently revised guidelines for managing hypertension and dyslipidemia in patients with diabetes have been incorporated into this guideline. An abridgment containing practical information on patient education and systematic management in the clinic was published separately.
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Affiliation(s)
- Jong Han Choi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
| | - Kyung Ae Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
| | - Joon Ho Moon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Suk Chon
- Department of Endocrinology and Metabolism, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Dae Jung Kim
- Department of Endocrinology and Metabolism, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea
| | - Hyun Jin Kim
- Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, Korea
| | - Nan Hee Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Ji A Seo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Mee Kyoung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jeong Hyun Lim
- Department of Food Service and Nutrition Care, Seoul National University Hospital, Seoul, Korea
| | - YoonJu Song
- Department of Food Science and Nutrition, The Catholic University of Korea, Bucheon, Korea
| | - Ye Seul Yang
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Hyeon Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - You-Bin Lee
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Junghyun Noh
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
| | - Kyu Yeon Hur
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jong Suk Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Youl Rhee
- Department of Endocrinology and Metabolism, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Hae Jin Kim
- Department of Endocrinology and Metabolism, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea
| | - Hyun Min Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Jung Hae Ko
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Nam Hoon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Chong Hwa Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea
| | - Jeeyun Ahn
- Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Tae Jung Oh
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Soo-Kyung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Jaehyun Kim
- Department of Pediatrics, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Eugene Han
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Sang-Man Jin
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Won Suk Choi
- Division of Infectious Diseases, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Min Kyong Moon
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Committee of Clinical Practice Guidelines
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
- Department of Endocrinology and Metabolism, College of Medicine, Kyung Hee University, Seoul, Korea
- Department of Endocrinology and Metabolism, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea
- Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Food Service and Nutrition Care, Seoul National University Hospital, Seoul, Korea
- Department of Food Science and Nutrition, The Catholic University of Korea, Bucheon, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea
- Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
- Department of Pediatrics, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
- Division of Infectious Diseases, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Korean Diabetes Association
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
- Department of Endocrinology and Metabolism, College of Medicine, Kyung Hee University, Seoul, Korea
- Department of Endocrinology and Metabolism, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea
- Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Food Service and Nutrition Care, Seoul National University Hospital, Seoul, Korea
- Department of Food Science and Nutrition, The Catholic University of Korea, Bucheon, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea
- Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
- Department of Pediatrics, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
- Division of Infectious Diseases, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
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20
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Wei R, Wang W, Huang X, Qiao J, Huang J, Xing C, Pan Q, Guo L. Evaluating the long-term cost-effectiveness of fixed-ratio combination insulin degludec/liraglutide (IDegLira) versus other treatment regimens in the chinese type 2 diabetes patients. Diabetol Metab Syndr 2023; 15:173. [PMID: 37598203 PMCID: PMC10439551 DOI: 10.1186/s13098-023-01141-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 06/23/2023] [Accepted: 07/22/2023] [Indexed: 08/21/2023] Open
Abstract
BACKGROUND AND AIMS To assess the cost-effectiveness of utilizing IDegLira in comparison to other treatment regimens ( liraglutide and degludec) in managing type 2 diabetes, taking into account the Chinese healthcare system's perspective. METHODS The clinical data were obtained from the randomized controlled trials (RCTs) of the DUAL I and DUAL II evidence studies that took place in China. To estimate the lifetime quality-adjusted life-years (QALYs) and direct medical costs of patients receiving different treatment strategies from a long-term perspective, the IQVIA CORE Diabetes Model version 9.0 (IQVIA, Basel, Switzerland) was utilized. The costs were evaluated from the perspective of the China National Health System. Future costs and clinical benefits were discounted annually at 5%, and sensitivity analyses were conducted. RESULTS IDegLira was projected to reduce the incidence of diabetes-related complications and improve quality-adjusted life expectancy (QALE) versus liraglutide and degludec. A survival benefit was observed with IDegLira over Liraglutide (0.073 years). Lifetime costs were lower by Chinese yuan (CNY) 27,945 on IDegLira than on Liraglutide therapy. A similar survival benefit was observed with IDegLira over degludec (0.068 years). Lifetime costs were lower by CNY 1196 on IDegLira than on degludec therapy. Therefore, IDegLira was found to be cost-effective versus liraglutide and degludec with incremental cost-effectiveness ratios of Dominant per QALY gained, respectively, under the threshold of three times the gross domestic product (GDP) per capita in China. CONCLUSION IDegLira is a cost-effective hypoglycemic treatment option that delivers positive clinical outcomes while also reducing costs for Chinese patients living with type 2 diabetes.
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Affiliation(s)
- Ran Wei
- Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, PR China
- Peking University Fifth School of Clinical Medicine, Beijing, China
| | - Weihao Wang
- Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, PR China
| | - Xiusheng Huang
- Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, PR China
| | - Jingtao Qiao
- Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, PR China
| | - Jinghe Huang
- Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, PR China
| | - Chang Xing
- Novo Nordisk (China) Pharmaceuticals Co., Ltd, Beijing, China
| | - Qi Pan
- Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, PR China.
| | - Lixin Guo
- Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, PR China.
- Peking University Fifth School of Clinical Medicine, Beijing, China.
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Silver HJ, Olson D, Mayfield D, Wright P, Nian H, Mashayekhi M, Koethe JR, Niswender KD, Luther JM, Brown NJ. Effect of the glucagon-like peptide-1 receptor agonist liraglutide, compared to caloric restriction, on appetite, dietary intake, body fat distribution and cardiometabolic biomarkers: A randomized trial in adults with obesity and prediabetes. Diabetes Obes Metab 2023; 25:2340-2350. [PMID: 37188932 PMCID: PMC10544709 DOI: 10.1111/dom.15113] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 03/13/2023] [Revised: 04/24/2023] [Accepted: 04/25/2023] [Indexed: 05/17/2023]
Abstract
AIMS To investigate the hypothesis that weight loss with the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide alone would lead to a greater reduction in the proportion of fat to lean tissue mass when compared to caloric restriction (CR) alone, as well as when compared to treatment with sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, that also enhances GLP-1 activity - to determine the independent effects of each treatment. METHODS A total of 88 adults with obesity and prediabetes were randomized to 14 weeks of intervention with CR (-390 kcal/d), liraglutide (1.8 mg/d), or the dipeptidyl peptidase-4 inhibitor sitagliptin (100 mg/d) as a weight-neutral comparator. Changes between groups in appetite and hunger ratings measured via visual analogue scales, dietary intakes, body weight, body composition via dual energy x-ray absorptiometry, and resting energy expenditure via indirect calorimetry were assessed using the Kruskal-Wallis test or Pearson's chi-squared test. RESULTS Weight loss ≥5% of baseline body weight occurred in 44% of participants in the CR group, 22% of the liraglutide group and 5% of the sitagliptin group (p = 0.02). The ratio of fat to lean mass decreased by 6.5% in the CR group, 2.2% in the liraglutide group, and 0% in the sitagliptin group (p = 0.02). Visceral fat reduced by 9.5% in the CR group, 4.8% in the liraglutide group, and 0% in the sitagliptin group (p = 0.04). A spontaneous reduction in dietary simple carbohydrates in the CR group was associated with improved homeostatic model assessment of insulin resistance score (HOMA-IR). CONCLUSIONS Although both liraglutide and CR are valuable strategies for cardiometabolic risk reduction, CR was associated with greater weight loss and more favourable improvements in body composition than treatment with liraglutide alone. Differences in the response to each of these interventions enables patients to be stratified to the most optimal intervention for their personal risk factors.
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Affiliation(s)
- Heidi J. Silver
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Department of Veteran Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA
| | - Dianna Olson
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Dustin Mayfield
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Patricia Wright
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Hui Nian
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Mona Mashayekhi
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - John R. Koethe
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Department of Veteran Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA
| | - Kevin D. Niswender
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Department of Veteran Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA
| | - James M. Luther
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Department of Veteran Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA
| | - Nancy J. Brown
- School of Medicine, Yale University, New Haven, Connecticut, USA
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Đekić D, Bojić M, Janež A, Klobučar S, Hadžimušović IG, Ković T, Mihalevska S. Effectiveness and Safety of iGlarLixi in People with Type 2 Diabetes in Adriatic Region Countries: ENSURE-ADR, a Real-World Study. Diabetes Ther 2023:10.1007/s13300-023-01407-3. [PMID: 37211579 DOI: 10.1007/s13300-023-01407-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 12/30/2022] [Accepted: 04/12/2023] [Indexed: 05/23/2023] Open
Abstract
INTRODUCTION The efficacy of iGlarLixi, a fixed-ratio combination of basal insulin glargine 100 units/mL (iGlar) and the short-acting GLP-1 RA lixisenatide (Lixi), was established in people with type 2 diabetes (T2D) who were advancing therapy from oral antidiabetic drugs (OADs) and basal insulin (BI). This retrospective study aimed to evaluate the effectiveness and safety of iGlarLixi using real-world data from people with T2D in the Adriatic region countries. METHODS This was a non-interventional, retrospective, multicenter, cohort study with the collection of pre-existing data at iGlarLixi initiation and after 6 months of treatment in real-world clinical and ambulatory settings. The primary outcome was the change in glycated hemoglobin (HbA1c) at 6 months after iGlarLixi initiation. Key secondary outcomes included the proportion of people achieving HbA1c < 7.0%, the effect of iGlarLixi on fasting plasma glucose (FPG), body weight and body mass index (BMI). RESULTS In this study, 262 participants (130 in Bosnia and Herzegovina, 72 in Croatia and 60 in Slovenia) initiated treatment with iGlarLixi. The participants had a mean ± SD age of 66.2 ± 7.9 years and the majority were women (58.0%). The mean baseline HbA1c was 8.9 ± 1.7% and the mean body weight was 94.3 ± 18.0 kg. After 6 months of treatment, the reduction in the mean HbA1c was statistically significant (1.11 ± 1.61%, 95% confidence internal [CI] 0.92, 1.31; p < 0.001), and the proportion of participants who achieved HbA1c < 7.0% had significantly increased from baseline (8.0-26.0%, p < 0.001). The change in mean FPG (mmol/L) levels was significant (2.7 ± 4.4 [95% CI 2.1, 3.2; p < 0.001]). The mean ± SD body weight and BMI were significantly reduced by 2.9 ± 4.3 kg (95% CI 2.3, 3.4; p < 0.001) and 1.3 ± 4.4 kg/m2 (95% CI 0.7, 1.8; p < 0.001), respectively. Two serious hypoglycemia episodes and one adverse gastrointestinal effect (nausea) were registered. CONCLUSIONS This real-world study demonstrated the effectiveness of iGlarLixi for improving glycemic control and decreasing body weight in people with T2D who need to advance therapy from OADs or insulin.
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Affiliation(s)
- Danijel Đekić
- University Clinical Centre of the Republic Srpska, Banja Luka, Bosnia and Herzegovina.
| | - Mirjana Bojić
- University Clinical Centre of the Republic Srpska, Banja Luka, Bosnia and Herzegovina
| | - Andrej Janež
- University Medical Center Ljubljana, Ljubljana, Slovenia
| | - Sanja Klobučar
- Clinical Hospital Center Rijeka, Medical Faculty, University of Rijeka, Rijeka, Croatia
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Vargas-Uricoechea H, Frias JP, Vargas-Sierra HD. Fixed-ratio Combinations (basal Insulin Plus GLP-1RA) In Type 2 Diabetes. an Analytical Review Of Pivotal Clinical Trials. Rev Diabet Stud 2023; 19:14-27. [PMID: 37185053 PMCID: PMC10082333 DOI: 10.1900/rds.2023.19.14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Indexed: 05/17/2023] Open
Abstract
In type 2 diabetes, therapeutic failure to the oral anti diabetics is frequent, the use of schemes with basal insulin or with multiple doses of insulin (basal insulin and short-acting insulins) are a widely accepted way to intensify therapy. The use of GLP-1 receptor agonists is another intensification strategy. The fixedratio combinations with molecules such as insulin degludec + liraglutide, and insulin glargine + lixisenatide have proven useful in intensifying treatment of individuals with type 2 diabetes. The purpose of this review was to evaluate and analyze the results of pivotal studies with both fixed-ratio combinations in individuals with type 2 diabetes, finding that, they are capable of achieving better glycemic control when compared with each of its components separately (with a lower risk of hypoglycemia vs basal insulin and lower risk of gastrointestinal adverse effects vs GLP-1 receptor agonists) in various clinical scenarios, especially in individuals who do not achieve control with oral antidiabetics or who do not achieve control with basal insulin (associated with oral antidiabetics) or in those under management with GLP-1RA plus oral antidiabetics.
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Affiliation(s)
- Hernando Vargas-Uricoechea
- Metabolic Diseases Study Group, Department of Internal Medicine, Universidad del Cauca, Popayán-Colombia
| | | | - Hernando David Vargas-Sierra
- Metabolic Diseases Study Group, Department of Internal Medicine, Universidad del Cauca, Popayán-Colombia. Fellowship in Endocrinology, Diabetes and Metabolism, Universidad Pontificia Bolivariana, Medellín-Colombia
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24
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Nomoto H. Fixed-ratio combinations of basal insulin and glucagon-like peptide-1 receptor agonists as a promising strategy for treating diabetes. World J Diabetes 2023; 14:188-197. [PMID: 37035222 PMCID: PMC10075027 DOI: 10.4239/wjd.v14.i3.188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 12/28/2022] [Revised: 01/13/2023] [Accepted: 02/09/2023] [Indexed: 03/15/2023] Open
Abstract
The maintenance of appropriate glycemic control is important for the prevention of diabetic complications in people with type 2 diabetes (T2D). Numerous oral antidiabetic drugs are now clinically available, but in particular, the introduction of injection regimens using insulin and/or glucagon-like peptide-1 receptor agonist (GLP-1RA)s represents promising step-up options for oral antidiabetic drug treatment. The recently licensed fixed-ratio combination (FRC) products, which comprise basal insulin and a GLP-1RA, have potent anti-hyperglycemic effects and reduce the undesirable side-effects of each component, such as body weight gain, hypoglycemia, and gastrointestinal symptoms. Two FRCs-insulin degludec/Liraglutide and insulin glargine/Lixisenatide-are now clinically available and, to date, several phase II/III trials have been conducted in particular groups of subjects with T2D. However, their utility in real-world clinical settings is of interest for most clinicians. Recently reported real-world clinical trials of these two FRCs in various situations have demonstrated their efficacy regarding glycemic control and the quality of life of people with T2D. Their long-term safety and efficacy require confirmation, but a treatment strategy that includes an FRC may be compatible with the concept of “well-balanced” therapy in certain groups of patients with T2D who have inadequate glycemic control.
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Affiliation(s)
- Hiroshi Nomoto
- Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Hokkaido, Japan
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25
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Bai S, Lin C, Jiao R, Cai X, Hu S, Lv F, Yang W, Zhu X, Ji L. Is the steady-state concentration, duration of action, or molecular weight of GLP-1RA associated with cardiovascular and renal outcomes in type 2 diabetes? Eur J Intern Med 2023; 109:79-88. [PMID: 36628824 DOI: 10.1016/j.ejim.2023.01.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 10/26/2022] [Revised: 01/02/2023] [Accepted: 01/05/2023] [Indexed: 01/09/2023]
Abstract
IMPORTANCE Disparities were found in the cardiovascular and renal outcomes among different glucagon-like peptide 1 receptor agonist (GLP-1RA) subtypes. However, whether the characteristics of GLP-1RA itself are associated with these disparities remains unclear. OBJECTIVE To assess the association between the steady-state concentration, duration of action, or molecular weight of GLP-1RA and the risks of cardiovascular and renal outcomes in patients with type 2 diabetes (T2D). DATA SOURCES PubMed, MEDLINE, EMBASE, Cochrane and Clinicaltrial.gov from inception to April 2022. STUDY SELECTION Randomized controlled trials (RCTs) investigating GLP-1RAs in patients with T2D were included. DATA EXTRACTION AND SYNTHESIS Literature screening and data extraction were performed independently by 2 researchers. The outcomes were computed as odds ratio (OR) and its 95% confidence interval (CI). Subgroup analyses were conducted according to steady-state concentration, duration of action and molecular weight of GLP-1RAs. MAIN OUTCOMES AND MEASURES Primary outcomes were major adverse cardiovascular events (MACE), composite renal outcome and all-cause mortality. RESULTS In all, 61 RCTs were included. When compared with non-GLP-1RA agents, GLP-1RAs with high steady-state concentration were associated with greater risk reduction in MACE (p for subgroup difference = 0.01) and the composite renal outcome (p for subgroup difference = 0.008) in patients with T2D. Greater risk reductions in MACE between GLP-1RA users versus non-GLP-RA users were observed in long acting stratum when compared with short acting stratum (p for subgroup difference = 0.04) in patients with T2D. The molecular weight of GLP-1RAs was not associated with the risk of cardiovascular and renal outcomes. CONCLUSIONS AND RELEVANCE GLP-1RAs with high steady-state concentrations might be associated with greater risk reductions in cardiovascular and renal outcomes in patients with T2D. Long acting GLP-1RAs might outperform short acting ones in reducing the risk of cardiovascular outcomes. These findings provided new insights for guiding the clinical applications of GLP-1RAs in patients with T2D.
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Affiliation(s)
- Shuzhen Bai
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Chu Lin
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Ruoyang Jiao
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Xiaoling Cai
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China.
| | - Suiyuan Hu
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Fang Lv
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Wenjia Yang
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Xingyun Zhu
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Linong Ji
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China.
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26
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Abusnana S, Al Awadi F, Aly H, Bashier A, Kumar Dhanwal D, Halasa T, Jallo M, Medina J, Singhal S. Switching to a fixed-ratio combination of insulin degludec/liraglutide (IDegLira) is associated with improved glycaemic control in a real-world population with type 2 diabetes mellitus in the United Arab Emirates: Results from the multicentre, prospective INTENSIFY study. Diabetes Res Clin Pract 2023; 196:110183. [PMID: 36436550 DOI: 10.1016/j.diabres.2022.110183] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 08/22/2022] [Revised: 11/01/2022] [Accepted: 11/18/2022] [Indexed: 11/25/2022]
Abstract
AIM Investigate the effectiveness of IDegLira, a fixed-ratio combination of insulin degludec/liraglutide, in a real-world setting in patients with type 2 diabetes mellitus in the United Arab Emirates. METHODS This non-interventional study enrolled adults switching to IDegLira from basal insulin (BI) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with/without concomitant oral antidiabetic drugs (OADs). Primary endpoint was change in HbA1c from baseline, assessed using a mixed model for repeated measurements. RESULTS Among 263 patients (BI ± OADs, n = 206; GLP-1 RA ± OADs, n = 57), mean baseline HbA1c was 9.29 % (78 mmol/mol). After 26 weeks, HbA1c was significantly reduced (BI ± OADs, -0.83 % [-9.0 mmol/mol] and GLP-1 RA ± OADs, -1.24 % [-13.5 mmol/mol]; both p < 0.0001). Fasting plasma glucose (FPG) was significantly reduced (-39.48 mg/dL [BI ± OADs] and -82.49 mg/dL [GLP-1 RA ± OADs]; both p < 0.0001). Before treatment initiation, 3/263 patients experienced ≥ 1 severe hypoglycaemic episode and 7/263 patients experienced ≥ 1 non-severe hypoglycaemic episode compared with 1/263 patients who had ≥ 1 severe and 1/263 who had ≥ 1 non-severe episode at end of study. Body weight decreased significantly among patients switching from BI ± OADs (-1.05 kg [p < 0.0001]). Treatment was well tolerated. CONCLUSIONS IDegLira significantly reduced HbA1c and FPG in this real-world setting, along with less frequent episodes of hypoglycaemia. Switching to IDegLira offers effective treatment intensification for type 2 diabetes patients with inadequate glycaemic control.
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Affiliation(s)
| | | | - Hazem Aly
- Novo Nordisk, Pharma Gulf, Dubai World Trade Centre, Dubai, United Arab Emirates
| | | | | | | | - Mahir Jallo
- Gulf Medical University & Thumbay University Hospital, Ajman, United Arab Emirates
| | | | - Sagar Singhal
- Novo Nordisk, Pharma Gulf, Dubai World Trade Centre, Dubai, United Arab Emirates
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27
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Ying X, Rongjiong Z, Kahaer M, Chunhui J, Wulasihan M. Therapeutic efficacy of liraglutide versus metformin in modulating the gut microbiota for treating type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease. Front Microbiol 2023; 14:1088187. [PMID: 36778868 PMCID: PMC9909237 DOI: 10.3389/fmicb.2023.1088187] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 11/04/2022] [Accepted: 01/09/2023] [Indexed: 01/27/2023] Open
Abstract
Metformin and liraglutide are used in the treatment of type 2 diabetes mellitus (T2DM) complicated with nonalcoholic fatty liver disease (NAFLD). Although these drugs can alter the intestinal microbiome, clinical data are required to explore their mechanisms of action. Using 16S sequencing technology, we analyzed and compared the intestinal bacterial community structure and function between patients before and after treatment (12 weeks) with the two drugs (metformin or liraglutide, n = 15) and healthy controls (n = 15). Moreover, combined with 19 clinical indices, the potential therapeutic mechanisms of the two drugs were compared. The studied clinical indices included those associated with islet β-cell function (FPG, FINS, HbA1c, and HOMA-IR), inflammation (TNF-α, IL-6, and APN), lipid metabolism (TC, TG, and LDL-C), and liver function (ALT, AST, and GGT); the values of all indices changed significantly after treatment (p < 0.01). In addition, the effect of the two drugs on the intestinal bacterial community varied. Liraglutide treatment significantly increased the diversity and richness of the intestinal bacterial community (p < 0.05); it significantly increased the relative abundances of Bacteroidetes, Proteobacteria, and Bacilli, whereas metformin treatment significantly increased the relative abundance of Fusobacteria and Actinobacteria (p < 0.05). Metformin treatment increased the complexity and stability of the intestinal bacterial network. However, liraglutide treatment had a weaker effect on the intestinal bacterial network, and the network after treatment was similar to that in healthy controls. Correlation matrix analysis between dominant genera and clinical indicators showed that the correlation between the bacterial community and islet β-cell function was stronger after liraglutide treatment, whereas the correlation between the bacterial community and inflammation-related factors was stronger after metformin treatment. Functional prediction showed that liraglutide could significantly affect the abundance of functional genes related to T2DM and NAFLD (p < 0.05), but the effect of metformin was not significant. This study is the first to report the changes in the intestinal bacterial community in patients treated with metformin or liraglutide and the differences between the mechanisms of action of metformin and liraglutide. Metformin or liraglutide has a therapeutic value in T2DM complicated with NAFLD, with liraglutide having a weaker effect on the intestinal bacterial community but a better therapeutic efficacy.
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Affiliation(s)
- Xing Ying
- Department of Comprehensive Internal Medicine Department 4, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Zheng Rongjiong
- Department of Infectious Disease, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Mayila Kahaer
- Department of Comprehensive Internal Medicine Department 4, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Jiang Chunhui
- Department of Comprehensive Internal Medicine Department 4, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Muhuyati Wulasihan
- Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China,*Correspondence: Muhuyati Wulasihan, ✉
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28
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Falcetta P, Nicolì F, Citro F, Ciccarone A, Garofolo M, Del Prato S, Bianchi C. De-intensification of basal-bolus insulin regimen after initiation of a GLP-1 RA improves glycaemic control and promotes weight loss in subjects with type 2 diabetes. Acta Diabetol 2023; 60:53-60. [PMID: 36166172 DOI: 10.1007/s00592-022-01974-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 08/09/2022] [Accepted: 09/12/2022] [Indexed: 01/07/2023]
Abstract
AIMS To evaluate the impact of adding a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in people with type 2 diabetes (T2D) in basal-bolus (BB) insulin regimen, on insulin requirement, HbA1c, weight loss up to 24 months. METHODS Data on subjects with T2D on BB who initiated a GLP-1 RA have been retrospectively collected. HbA1c, body weight, and insulin dose were recorded at baseline, 6, 12, and 24 months after initiation of GLP-1 RA therapy. A linear mixed model for repeated measures was used to evaluate the changes in HbA1c, body weight, and insulin requirement over time. RESULTS We included 156 subjects (63.5% males; age 62 ± 11 years, HbA1c 70 ± 22.0 mmol/mol; 8.6 ± 4.2%). Compared to baseline, HbA1c and body weight were significantly lower at 6 months after introducing a GLP-1RA and remained stable up to 24 months (all p < 0.0001 vs. baseline). At 24 months, 81% of subjects discontinued prandial insulin, while 38.6% discontinued basal insulin as well. Insulin requirement at baseline (aOR 0.144; 95% CI, 0.046-0.456; P = 0.001) was the only significant predictor of prandial insulin discontinuation. CONCLUSIONS Replacing prandial insulin with GLP-1 RA is a valuable strategy to simplify the BB insulin regimen while improving glycaemic control and promoting weight loss in subjects with T2D.
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Affiliation(s)
- Pierpaolo Falcetta
- Department of Clinical and Experimental Medicine, University of Pisa, 56124, Pisa, Italy
| | - Francesca Nicolì
- Department of Clinical and Experimental Medicine, University of Pisa, 56124, Pisa, Italy
| | - Fabrizia Citro
- Department of Clinical and Experimental Medicine, University of Pisa, 56124, Pisa, Italy
| | - Annamaria Ciccarone
- Department of Medicine, University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy
| | - Monia Garofolo
- Department of Clinical and Experimental Medicine, University of Pisa, 56124, Pisa, Italy
| | - Stefano Del Prato
- Department of Clinical and Experimental Medicine, University of Pisa, 56124, Pisa, Italy
| | - Cristina Bianchi
- Department of Medicine, University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
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29
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ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, Collins BS, Hilliard ME, Isaacs D, Johnson EL, Kahan S, Khunti K, Leon J, Lyons SK, Perry ML, Prahalad P, Pratley RE, Seley JJ, Stanton RC, Gabbay RA, on behalf of the American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2023. Diabetes Care 2023; 46:S140-S157. [PMID: 36507650 PMCID: PMC9810476 DOI: 10.2337/dc23-s009] [Citation(s) in RCA: 480] [Impact Index Per Article: 240.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Indexed: 12/15/2022]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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30
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Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, Rosas SE, Del Prato S, Mathieu C, Mingrone G, Rossing P, Tankova T, Tsapas A, Buse JB. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2022; 65:1925-1966. [PMID: 36151309 PMCID: PMC9510507 DOI: 10.1007/s00125-022-05787-2] [Citation(s) in RCA: 400] [Impact Index Per Article: 133.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 08/02/2022] [Accepted: 08/18/2022] [Indexed: 01/11/2023]
Abstract
The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the previous consensus statements on the management of hyperglycaemia in type 2 diabetes in adults, published since 2006 and last updated in 2019. The target audience is the full spectrum of the professional healthcare team providing diabetes care in the USA and Europe. A systematic examination of publications since 2018 informed new recommendations. These include additional focus on social determinants of health, the healthcare system and physical activity behaviours including sleep. There is a greater emphasis on weight management as part of the holistic approach to diabetes management. The results of cardiovascular and kidney outcomes trials involving sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, including assessment of subgroups, inform broader recommendations for cardiorenal protection in people with diabetes at high risk of cardiorenal disease. After a summary listing of consensus recommendations, practical tips for implementation are provided.
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Affiliation(s)
- Melanie J Davies
- Leicester Diabetes Research Centre, University of Leicester, Leicester, UK.
- Leicester National Institute for Health Research (NIHR) Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK.
| | - Vanita R Aroda
- Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Billy S Collins
- National Heart, Lung, and Blood Institute, Bethesda, MD, USA
| | | | - Jennifer Green
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA
| | - Nisa M Maruthur
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Sylvia E Rosas
- Kidney and Hypertension Unit, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
| | - Stefano Del Prato
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Chantal Mathieu
- Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium
| | - Geltrude Mingrone
- Università Cattolica del Sacro Cuore, Rome, Italy
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Division of Diabetes and Nutritional Sciences, School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, London, UK
| | - Peter Rossing
- Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Tsvetalina Tankova
- Department of Endocrinology, Medical University - Sofia, Sofia, Bulgaria
| | - Apostolos Tsapas
- Diabetes Centre, Clinical Research and Evidence-based Medicine Unit, Aristotle University Thessaloniki, Thessaloniki, Greece
- Harris Manchester College, University of Oxford, Oxford, UK
| | - John B Buse
- University of North Carolina School of Medicine, Chapel Hill, NC, USA.
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31
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Tramunt B, Disse E, Chevalier N, Bordier L, Cazals L, Dupuy O, Marre M, Matar O, Meyer L, Noilhan C, Sanz C, Valensi P, Velayoudom FL, Gautier JF, Gourdy P. Initiation of the Fixed Combination IDegLira in Patients with Type 2 Diabetes on Prior Injectable Therapy: Insights from the EASY French Real-World Study. Diabetes Ther 2022; 13:1947-1963. [PMID: 36331712 PMCID: PMC9663793 DOI: 10.1007/s13300-022-01327-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 09/02/2022] [Accepted: 10/17/2022] [Indexed: 11/06/2022] Open
Abstract
INTRODUCTION Combining basal insulin (BI) with glucagon-like peptide-1 receptor agonist (GLP-1RA) is recognized as a relevant option to optimize glucose control in type 2 diabetes (T2D). The EASY real-world study aimed to evaluate the modalities of initiation and the effectiveness of the insulin Degludec plus Liraglutide (IDegLira) fixed-ratio combination in the French health care system. METHODS A retrospective analysis included all patients with T2D and prior injectable therapy (GLP1-RA and/or insulin) who started treatment with IDegLira from September 2016 to December 2017 in 11 French diabetes centers. Baseline characteristics, reasons for IDegLira initiation, and modes of implementation were collected from the medical records. Changes in HbA1c and body weight were determined in patients with available follow-up data (nearest 6-month visit). RESULTS IDegLira was initiated in 629 patients previously treated with GLP-1RA alone (11.6%), insulin alone (31.5% including 16.5% with BI and 14.9% with multiple daily injections [MDI]) or a free combination of GLP-1RA and insulin (56.9% including 44.8% with BI and 12.1% with MDI), associated or not with oral agents. IDegLira starting dose (mean of 29 ± 11 dose steps) most often exceeded the recommended dose, and was significantly correlated with prior BI but not GLP-1RA dosage. At initiation, mean age, body mass index (BMI) and HbA1c were 60.1 ± 10.2 years, 33.4 ± 6.2 kg/m2 and 8.8 ± 1.7%, respectively. In 461 patients with available follow-up (median 178 days), HbA1c decreased in all subgroups submitted to treatment intensification (- 1.7 ± 1.8% [p < 0.0001], - 1.2 ± 1.8% [p < 0.001] and - 0.8 ± 1.8% [p = 0.0026] in patients with prior GLP-1RA, BI or MDI therapy, respectively) but also in those switching from BI and GLP-1RA free combination (- 0.2 ± 0.9%, p = 0.0419). Significant body weight gain occurred in patients previously treated with GLP-1RA alone (+ 1.5 ± 5.8 kg, p = 0.0572) or combined to BI (+ 1.0 ± 3.1 kg, p < 0.0001) while those on BI (- 1.4 ± 4.6 kg, p = 0.0139) or MDI (- 1.4 ± 5.0 kg, p = 0.0484) experienced weight loss. CONCLUSIONS While providing new information on the use of IDegLira in the French healthcare system, these data confirm the effectiveness of this fixed-ratio combination in the management of T2D.
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Affiliation(s)
- Blandine Tramunt
- Service de Diabétologie, Maladies Métaboliques et Nutrition, CHU et Université de Toulouse, TSA 50032, 31059, Toulouse Cedex 9, France
- Institut des Maladies Métaboliques et Cardiovasculaires, UMR1297 INSERM/UT3, Toulouse, France
| | - Emmanuel Disse
- Service d'Endocrinologie, Diabète et Nutrition, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Lyon, France
| | - Nicolas Chevalier
- Université Côte d'Azur, Centre Hospitalier Universitaire, INSERM U1065, C3M, Nice, France
| | - Lyse Bordier
- Service d'Endocrinologie, Hôpital d'instruction des Armées Begin, Saint-Mandé, France
| | - Laurent Cazals
- Service de Diabétologie, Maladies Métaboliques et Nutrition, CHU et Université de Toulouse, TSA 50032, 31059, Toulouse Cedex 9, France
| | - Olivier Dupuy
- Service de Diabétologie et Endocrinologie, Groupe Hospitalier Saint-Joseph, Paris, France
| | - Michel Marre
- Clinique Ambroise Paré, Neuilly-sur-Seine, France
| | - Odette Matar
- Service d'Endocrinologie, Diabétologie et Nutrition, Hôpital Bichat, Paris, France
| | - Laurent Meyer
- Service d'Endocrinologie, Diabète et Maladies Métaboliques, CHU de Strasbourg, Strasbourg, France
| | - Chloé Noilhan
- Service de Diabétologie, Maladies Métaboliques et Nutrition, CHU et Université de Toulouse, TSA 50032, 31059, Toulouse Cedex 9, France
| | - Caroline Sanz
- Cabinet d'Endocrinologie, de Diabétologie et de Nutrition, Clinique Pasteur, Toulouse, France
| | - Paul Valensi
- Unit of Endocrinology, Diabetology and Nutrition, Jean Verdier Hospital, Paris Nord University, Bondy, France
| | | | - Jean-François Gautier
- Service de Diabétologie et d'Endocrinologie, Hôpital Lariboisière, AP-HP, Paris Cité, INSERM 1151, Paris, France
- Université Paris Cité, INSERM UMR-S1151, CNRS UMR-S8253, Institut Necker Enfants Malades, 75015, Paris, France
| | - Pierre Gourdy
- Service de Diabétologie, Maladies Métaboliques et Nutrition, CHU et Université de Toulouse, TSA 50032, 31059, Toulouse Cedex 9, France.
- Institut des Maladies Métaboliques et Cardiovasculaires, UMR1297 INSERM/UT3, Toulouse, France.
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Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, Rosas SE, Del Prato S, Mathieu C, Mingrone G, Rossing P, Tankova T, Tsapas A, Buse JB. Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2022; 45:2753-2786. [PMID: 36148880 PMCID: PMC10008140 DOI: 10.2337/dci22-0034] [Citation(s) in RCA: 673] [Impact Index Per Article: 224.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 08/02/2022] [Accepted: 08/04/2022] [Indexed: 02/07/2023]
Abstract
The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the previous consensus statements on the management of hyperglycemia in type 2 diabetes in adults, published since 2006 and last updated in 2019. The target audience is the full spectrum of the professional health care team providing diabetes care in the U.S. and Europe. A systematic examination of publications since 2018 informed new recommendations. These include additional focus on social determinants of health, the health care system, and physical activity behaviors, including sleep. There is a greater emphasis on weight management as part of the holistic approach to diabetes management. The results of cardiovascular and kidney outcomes trials involving sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists, including assessment of subgroups, inform broader recommendations for cardiorenal protection in people with diabetes at high risk of cardiorenal disease. After a summary listing of consensus recommendations, practical tips for implementation are provided.
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Affiliation(s)
- Melanie J. Davies
- Leicester Diabetes Research Centre, University of Leicester, Leicester, U.K
- Leicester National Institute for Health Research Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, U.K
| | - Vanita R. Aroda
- Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | | | | | - Jennifer Green
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC
| | - Nisa M. Maruthur
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Sylvia E. Rosas
- Kidney and Hypertension Unit, Joslin Diabetes Center, Harvard Medical School, Boston, MA
| | - Stefano Del Prato
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Chantal Mathieu
- Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium
| | - Geltrude Mingrone
- Università Cattolica del Sacro Cuore, Rome, Italy
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Division of Diabetes and Nutritional Sciences, School of Cardiovascular and Metabolic Medicine and Sciences, King’s College London, London, U.K
| | - Peter Rossing
- Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | | | - Apostolos Tsapas
- Diabetes Centre, Clinical Research and Evidence-Based Medicine Unit, Aristotle University Thessaloniki, Thessaloniki, Greece
- Harris Manchester College, University of Oxford, Oxford, U.K
| | - John B. Buse
- University of North Carolina School of Medicine, Chapel Hill, NC
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Szépkúti S, Bandur S, Kovács G, Ferenci T, Svébis MM, Turbucz P, Tabák ÁG. Real-world effectiveness of IDegLira compared with intensified conventional insulin therapy in adults with type 2 diabetes: a retrospective cohort study. BMC Endocr Disord 2022; 22:229. [PMID: 36104712 PMCID: PMC9476268 DOI: 10.1186/s12902-022-01139-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 05/30/2022] [Accepted: 08/26/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND IDegLira is a fixed-ratio combination of insulin degludec and liraglutide with proven efficacy against simpler regimens and non-inferiority against basal-bolus insulin therapy. However, the evaluation of its real-world effectiveness is hindered by technical issues and requires further exploration. Thus we aimed to compare effectiveness of insulin degludec/liraglutide (IDegLira) versus intensified conventional insulin therapy (ICT) for type 2 diabetes in a real-world setting. METHODS This retrospective cohort study from an outpatient clinic in Hungary included people who initiated IDegLira due to inadequate glycaemic control (HbA1c > 7.0% [53.0 mmol/mol]) with oral and/or injectable antidiabetic drugs. Data were compared with a historical cohort who initiated ICT. Outcomes included HbA1c, body weight, and hypoglycaemia differences over 18 months of follow-up. RESULTS Data were included from 227 and 72 people who initiated IDegLira and ICT, respectively. Estimated mean difference (MD) in HbA1c at 18 months favoured IDegLira versus ICT (MD 0.60, 95% CI 0.88-0.32 [MD 6.6 mmol/mol, 95% CI 9.6-3.5]). More people reached target HbA1c ≤7.0% (53.0 mmol/mol) with IDegLira than ICT (odds ratio 3.36, 95% CI 1.52-7.42). IDegLira treatment was associated with weight loss compared with gain for ICT (MD 6.7 kg, 95% CI 5.0-8.5). The hazard ratio for hypoglycaemia comparing IDegLira with ICT was 0.18 (95% CI 0.08-0.49). CONCLUSIONS Treatment with IDegLira over 18 months resulted in greater HbA1c reductions, weight loss versus gain, and a lower rate of hypoglycaemia versus ICT in people with type 2 diabetes.
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Affiliation(s)
- Sándor Szépkúti
- Diabetology, Pest County Flór Ferenc Hospital, Kistarcsa, Hungary
| | - Szilvia Bandur
- Diabetology, Pest County Flór Ferenc Hospital, Kistarcsa, Hungary
| | - Gábor Kovács
- Diabetology, Pest County Flór Ferenc Hospital, Kistarcsa, Hungary
| | - Tamás Ferenci
- Physiological Controls Research Center, Óbuda University, Budapest, Hungary
- Department of Statistics, Corvinus University of Budapest, Budapest, Hungary
| | - Márk M. Svébis
- Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, Üllői út 26, Budapest, H1085 Hungary
| | - Piroska Turbucz
- Diabetology, Pest County Flór Ferenc Hospital, Kistarcsa, Hungary
| | - Ádám G. Tabák
- Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, Üllői út 26, Budapest, H1085 Hungary
- Department of Public Health, Semmelweis University Faculty of Medicine, Üllői út 26, Budapest, H1085 Hungary
- Department of Epidemiology and Public Health, University College London, London, UK
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Mehta R, Billings LK, Liebl A, Vilsbøll T. Transitioning from basal-bolus or premix insulin therapy to a combination of basal insulin and glucagon-like peptide-1 receptor agonist in people with type 2 diabetes. Diabet Med 2022; 39:e14901. [PMID: 35708737 PMCID: PMC9542161 DOI: 10.1111/dme.14901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 11/18/2021] [Revised: 04/29/2022] [Accepted: 06/14/2022] [Indexed: 11/27/2022]
Abstract
AIMS Two fixed-ratio combinations (FRCs) of basal insulin and glucagon-like peptide-1 receptor agonist (GLP-1RA) are available for once-daily use in adults with type 2 diabetes. We aimed to review the clinical evidence for the efficacy and safety of changing treatment from a basal-bolus insulin (BBI) regimen or a premix insulin to these combination treatments (fixed-ratio or loose) and provide expert opinion on the practicalities of making such a change. METHODS Relevant clinical and trial evidence and general review articles were identified through a literature review of ProQuest (comprising BIOSIS Previews®, Current Contents® Search, Embase® and MEDLINE®) for articles published between 2009 and 2021. RESULTS We identified nine articles reporting the results of FRCs, and seven articles reporting results of loose combinations of basal insulin and GLP-1RAs, in people who transitioned treatment from BBI or premix regimens. In most trials, combination treatment led to improved or equivalent glycaemic control, and a reduction in body weight or BMI, versus the original regimens. Some trials reported a reduction in total insulin dose. A few trials reported reduced or unchanged hypoglycaemia rates, or increased patient satisfaction, with combination therapy where these endpoints were examined. We provide guidance on transitioning of treatment and the patient types most likely to benefit. CONCLUSIONS In people not achieving glycaemic control with BBI or premix insulin regimens, an FRC or loose combination of basal insulin and GLP-1RA may improve control, decrease the risk of body weight gain or hypoglycaemia and reduce the complexity of treatment.
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Affiliation(s)
- Roopa Mehta
- Unidad de Investigación en Enfermedades Metabólicas, Departamento de Endocrinología y MetabolismoInstituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico CityMexico
| | - Liana K. Billings
- Division of Endocrinology and MetabolismNorthShore University HealthSystemSkokieIllinoisUSA
- Department of MedicineUniversity of Chicago Pritzker School of MedicineSkokieIllinoisUSA
| | - Andreas Liebl
- Center for Diabetes and Metabolism, m&i‐FachklinikBad HeilbrunnGermany
| | - Tina Vilsbøll
- Steno Diabetes Center Copenhagen, Gentofte HospitalGentofteDenmark
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Fadini GP, Buzzetti R, Fittipaldi MR, D’Incau F, Da Porto A, Girelli A, Simoni L, Lastoria G, Consoli A. IDegLira for the Real-World Treatment of Type 2 Diabetes in Italy: Protocol and Interim Results from the REX Observational Study. Diabetes Ther 2022; 13:1483-1497. [PMID: 35717487 PMCID: PMC9309107 DOI: 10.1007/s13300-022-01287-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 04/26/2022] [Accepted: 06/01/2022] [Indexed: 11/16/2022] Open
Abstract
INTRODUCTION IDegLira was shown to maintain glycemic control while reducing risk of hypoglycemia and body weight gain. The REX study was designed to generate real-world evidence on the use of IDegLira in Italian clinical practice in two different subgroups of patients, those switching to IDegLira from a basal insulin-supported oral therapy (BOT group) and those from a basal plus bolus insulin regimen (BB group). METHODS Adult patients with T2D diagnosed for at least 12 months and having started IDegLira 2-3 months prior to enrolment, coming from a BOT or BB regimen, were enrolled in this multicenter observational prospective cohort study conducted in 28 Italian centers. This paper presents the methodological framework of the REX study and provides the interim analysis results describing the patients' baseline characteristics and the clinical reasons for IDegLira treatment initiation. RESULTS Of the 360 patients enrolled in the REX study, 331 were considered eligible for this interim analysis, 76.4% in the BOT and 23.6% in the BB group. Mean (SD) HbA1c was 8.5% (1.4) in the BOT and 8.2% (1.7) in the BB group. The most common T2D complications were diabetic macroangiopathy and diabetic nephropathy in both groups. The median (interquartile range) insulin daily dose before IDegLira was 15.0 (10.0-20.0) units in the BOT group and 42 (30.0-52.0) in the BB group. Oral antidiabetics were taken by 98% and 51.3% of patients, respectively. The main reason for switching to IDegLira was the inadequate glycemic control in the BOT group (86% of patients), and the intent to simplify the treatment in the BB group (66.7%). CONCLUSIONS IdegLira is initiated after BOT in inadequately controlled patients to improve glycemic control, whereas in BB patients it is used to simplify the therapeutic regimen. Final results of the REX study will shed light on patients' outcomes after IdegLira treatment under routine clinical care.
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Affiliation(s)
- Gian Paolo Fadini
- Division of Metabolic Diseases, Department of Medicine, Padova Hospital, University of Padova, Padua, Italy
| | - Raffaella Buzzetti
- Department of Experimental Medicine, Sapienza University of Rome - Policlinico Umberto I Hospital, Rome, Italy
| | - Maria Rosa Fittipaldi
- Internal Medicine Unit, San Francesco d’Assisi Hospital, Oliveto Citra, Salerno Italy
| | - Ferruccio D’Incau
- Center of Diabetology, S. Maria del Prato Hospital, Feltre, Belluno Italy
| | - Andrea Da Porto
- Division of Internal Medicine, Department of Medicine, University of Udine, Udine, Italy
| | - Angela Girelli
- Diabetes Care Unit, Spedali Civili Hospital, Brescia, Italy
| | - Lucia Simoni
- MediNeos Observational Research, IQVIA Company, Modena, Italy
| | | | - Agostino Consoli
- Department of Medicine and Aging Sciences, Centro Scienze Dell’Invecchiamento-Medicina Traslazionale (CeSI-MeT), University G. D’Annunzio, Chieti, Italy
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Li H, Yang A, Zhao S, Chow EYK, Javanbakht M, Li Y, Lin D, Xu L, Zang D, Wang K, Ma L. Continuous Subcutaneous Insulin Infusion (CSII) Combined with Oral Glucose-Lowering Drugs in Type 2 Diabetes: A Systematic Review and Network Meta-Analysis of Randomized, Controlled Trials. Pharmaceuticals (Basel) 2022; 15:953. [PMID: 36015100 PMCID: PMC9412496 DOI: 10.3390/ph15080953] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 06/08/2022] [Revised: 07/13/2022] [Accepted: 07/24/2022] [Indexed: 02/04/2023] Open
Abstract
The clinical efficacy of continuous subcutaneous insulin infusion (CSII) therapy combined with six classes of oral glucose-lowering drugs (GLDs) (TZDs/metformin/acarbose/GLP-1 receptor agonist/SGLT-2 inhibitor/DPP-4 inhibitor) was evaluated by a network meta-analysis to provide an evidence-based reference in making a clinical decision on CSII combined with drugs in the treatment of type 2 diabetes. Data were retrieved from eight databases: the Chinese Journal Full-Text Database (CNKI), VIP Chinese Science and Technology Periodicals Full-Text Database (VP-CSFD), Wanfang Data Journal Paper Resource (WANFANG), China Biomedical Database (CBM), PubMed, Embase, Cochrane Library, and Web of Science. The retrieval period dated from the library's construction to 27 June 2021. The search was for randomized, controlled trial studies (RCT) on insulin infusion (CSII) combined with oral hypoglycemic drugs (TZDs/metformin/acarbose/GLP-1 receptor agonist/SGLT-2 inhibitor/DPP-4 inhibitor) in the treatment of type 2 diabetes. Quality evaluation and data extraction were performed on the studies included, and network meta-analysis was performed with R4.0.1 software. A total of 56 publications was included in the final network meta-analysis, with a total sample size of 4395. Results based on the network meta-analysis were that CSII combined with a metformin works best on fasting blood glucose (FBG) and 2 h postprandial blood glucose (2hPG) and improves insulin resistance (lower HOMA-IR levels). CSII combined with a DPP-4 inhibitor had the best clinical effect in reducing glycosylated hemoglobin levels. Treatment with CSII combined with a DPP-4 inhibitor was the fastest way to achieve the blood glucose standard. In terms of insulin dosage, an insulin pump (CSII) combined with the GLP-1 receptor agonist can significantly reduce insulin dosage. Network meta-analysis evidence suggests that an insulin infusion (CSII) combined with oral hypoglycemic drugs can improve clinical efficacy in controlling blood sugar and improving insulin resistance, insulin dosage, and standard time. However, the most outstanding performance was that of insulin infusion (CSII) combined with metformin, which had the best clinical effect in controlling blood sugar and improving insulin resistance.
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Affiliation(s)
- Hui Li
- Department of endocrine, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi 830000, China; (H.L.); (Y.L.); (L.X.); (D.Z.)
| | - Aimin Yang
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong 999077, China; (A.Y.); (E.Y.C.)
| | - Shi Zhao
- JC School of Public Health and Primary Care, Chinese University of Hong Kong, Hong Kong 999077, China;
| | - Elaine YK Chow
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong 999077, China; (A.Y.); (E.Y.C.)
| | - Mohammad Javanbakht
- Nephrology and Urology Research Center, Baqiyatallah University of Medical Sciences, Tehran 1435916471, Iran;
| | - Yinhui Li
- Department of endocrine, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi 830000, China; (H.L.); (Y.L.); (L.X.); (D.Z.)
| | - Dandan Lin
- Department of Medical Engineering and Technology, Xinjiang Medical University, Urumqi 830011, China;
| | - Lijuan Xu
- Department of endocrine, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi 830000, China; (H.L.); (Y.L.); (L.X.); (D.Z.)
| | - Deng Zang
- Department of endocrine, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi 830000, China; (H.L.); (Y.L.); (L.X.); (D.Z.)
| | - Kai Wang
- Department of Medical Engineering and Technology, Xinjiang Medical University, Urumqi 830011, China;
| | - Li Ma
- Department of endocrine, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi 830000, China; (H.L.); (Y.L.); (L.X.); (D.Z.)
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Kheniser K, Aminian A, Kashyap SR. Effects of Metabolic Medicine and Metabolic Surgery on Patient-Reported Outcomes Among Patients with Type 2 Diabetes. Metab Syndr Relat Disord 2022; 20:497-508. [PMID: 35881869 DOI: 10.1089/met.2022.0039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 11/13/2022] Open
Abstract
The assessment and management of patient-reported outcomes (PROs) is considered secondary to that of cardiometabolic outcomes. When assessed, health-related quality of life (HRQOL), a PRO, can yield pertinent information that cannot be obtained from cardiometabolic assessments. For instance, physical and mental distress can be quantified and treated. Moreover, treatment convenience and satisfaction can be gaged. Behavioral modification, bariatric surgery, and pharmacotherapy can improve PROs. Typically, HRQOL is responsive to changes in weight. Specifically, weight loss and weight gain are associated with positive and negative changes in quality of life, respectively. In addition, patient satisfaction can be influenced by glycemic control. Therefore, hypoglycemia and hyperglycemic episodes can negatively affect patient satisfaction. When managing type 2 diabetes (T2D), it is important to consider how therapies impact PROs. Generally, changes in clinical outcomes mirror changes in PROs. To best manage T2D, integrating the assessment of PROs with clinical outcomes is needed.
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Affiliation(s)
- Karim Kheniser
- Department of General Surgery, Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Ali Aminian
- Department of General Surgery, Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Sangeeta R Kashyap
- Department of Endocrinology and Metabolism, Cleveland Clinic, Cleveland, Ohio, USA
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Efficacy of IDegLira Versus IDegAsp Therapy in Patients with Type 2 Diabetes: A Randomized Crossover Study by isCGM. Adv Ther 2022; 39:2688-2700. [PMID: 35403949 PMCID: PMC9122848 DOI: 10.1007/s12325-022-02138-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 02/02/2022] [Accepted: 03/17/2022] [Indexed: 01/03/2023]
Abstract
Introduction We aimed to compare the efficacy of insulin degludec/insulin aspart (IDegAsp) and insulin degludec/liraglutide (IDegLira) in controlling glucose fluctuation and suppressing postprandial glucose levels using intermittently scanned continuous glucose monitoring. Methods Twenty-four patients with type 2 diabetes mellitus were randomly allocated to receive either IDegLira or IDegAsp followed by IDegAsp or IDegLira, respectively. A crossover study was conducted with intermittently scanned continuous glucose monitoring. We compared the postprandial blood glucose level, time in range, and time below range from a 3-day intermittently scanned continuous glucose monitoring period for each treatment group. Results The time in range was significantly higher in IDegLira than in IDegAsp. Postprandial glucose levels 90 and 120 min after breakfast and 60, 90, and 120 min after lunch were significantly lower for IDegLira than for IDegAsp. However, postprandial glucose levels 90 and 120 min after supper were significantly lower for IDegAsp than for IDegLira. There was no significant difference in the time below range between IDegLira and IDegAsp. Conclusion IDegLira was more effective in treating type 2 diabetes mellitus than IDegAsp, as indicated by a higher time in range and lower postprandial glucose level at breakfast and lunch. This study was registered with the University Hospital Medical Information Network Clinical Trial Registry (UMIN 000039221). Supplementary Information The online version contains supplementary material available at 10.1007/s12325-022-02138-w.
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Liu H, Luo B, Chen X, Ingwersen SH, Jia T, Vestergård Jacobsen L, Hu P. Preserved pharmacokinetics and pharmacodynamics of insulin degludec and liraglutide when administered as insulin degludec/liraglutide in a Chinese population. J Diabetes Investig 2022; 13:652-656. [PMID: 34797962 PMCID: PMC9017614 DOI: 10.1111/jdi.13716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 08/11/2021] [Revised: 11/10/2021] [Accepted: 11/17/2021] [Indexed: 11/30/2022] Open
Abstract
We report the findings of a single-dose, randomized, three-period cross-over, clinical trial in healthy Chinese individuals (n = 24) comparing the pharmacokinetics of insulin degludec/liraglutide (IDegLira) with its individual components. Furthermore, we report a population pharmacokinetic analysis of a 26-week, phase III, treat-to-target, randomized trial of 720 Chinese individuals with type 2 diabetes. Participants were randomized to IDegLira, degludec or liraglutide, all once daily with metformin. The pharmacokinetic profiles of IDegLira were similar to its individual components. Dose proportionality was indicated for both IDegLira components. Although there were no relevant covariate effects on degludec exposure, liraglutide exposure was inversely correlated with bodyweight. In conclusion, for the Chinese population, the pharmacokinetics of the fixed-ratio combination IDegLira is similar to that of its individual components.
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Affiliation(s)
- Hongzhong Liu
- Clinical Pharmacology Research CenterChinese Academy of Medical Sciences & Peking Union Medical CollegePeking Union Medical College HospitalBeijingChina
- Beijing Key Laboratory of Clinical Pharmacokinetics & Pharmacodynamics Investigation for Innovative DrugsPeking Union Medical College HospitalBeijingChina
| | - Bin Luo
- Novo Nordisk China Pharmaceuticals Co. LtdBeijingChina
| | - Xia Chen
- Clinical Pharmacology Research CenterChinese Academy of Medical Sciences & Peking Union Medical CollegePeking Union Medical College HospitalBeijingChina
- National Clinical Research Center for Neurological DiseasesClinical Trial CenterBeijing Tiantan HospitalBeijingChina
| | | | | | | | - Pei Hu
- Clinical Pharmacology Research CenterChinese Academy of Medical Sciences & Peking Union Medical CollegePeking Union Medical College HospitalBeijingChina
- Beijing Key Laboratory of Clinical Pharmacokinetics & Pharmacodynamics Investigation for Innovative DrugsPeking Union Medical College HospitalBeijingChina
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Shibuki K, Shimada S, Aoyama T. Meta-analysis of seven heterogeneous studies on liraglutide add-on therapy in patients with type 2 diabetes mellitus treated with insulin. Diabetes Metab Syndr 2022; 16:102474. [PMID: 35378386 DOI: 10.1016/j.dsx.2022.102474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 12/21/2021] [Revised: 03/23/2022] [Accepted: 03/25/2022] [Indexed: 12/01/2022]
Abstract
BACKGROUND AND AIMS Clinical trials indicate the efficacy of add-on therapy using incretin-related drugs to treat type 2 diabetes mellitus (DM) inadequately controlled by insulin. However, heterogeneity exists among these studies. Baseline body mass index (BMI) accounts for the heterogeneity of add-on therapy with dipeptidyl peptidase-4 (DPP-4) inhibitors and the associated higher BMI with a lower efficacy. The efficacy of add-on therapy with glucagon-like peptide-1 (GLP-1) receptor agonists remains unclear. METHODS We performed a meta-analysis of randomized controlled trials of ≥12 weeks reporting the endpoint of adjusted mean change in hemoglobin A1c levels (AMΔHbA1c) or hypoglycemia incidence. Patients with type 2 DM treated with insulin alone or with metformin for at least 8 weeks before the study treatment were included. The intervention group received liraglutide co-administered with insulin or a fixed-dose combination. The control group received a placebo or insulin. Covariates included five baseline parameters (HbA1c, fasting plasma glucose, BMI, type 2 DM duration, and treatment duration). RESULTS Seven studies (2067 patients) were selected. AMΔHbA1c was -1.00% (95% confidence interval [CI]: -1.21 to -0.78, I2 = 74.7%). The odds ratio for hypoglycemia incidence was 0.97 (95% CI: 0.50-1.87, I2 = 81.9%). Covariates did not account for the heterogeneity in AMΔHbA1c or hypoglycemia incidence. CONCLUSIONS Liraglutide add-on therapy reduced HbA1c levels without increasing hypoglycemia incidence, independent of BMI, in insulin non-responders with type 2 DM. GLP-1 receptor agonists may be more suitable than DPP-4 inhibitors for add-on therapy in patients with high BMI. REGISTRATION NUMBER PROSPERO #CRD42021178888.
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Affiliation(s)
- Katsuya Shibuki
- Department of Pharmacy, Tokyo University of Science, 2641 Yamazaki, Noda, 278-8510, Japan.
| | - Shuji Shimada
- Department of Pharmacy, Tokyo University of Science, 2641 Yamazaki, Noda, 278-8510, Japan.
| | - Takao Aoyama
- Department of Pharmacy, Tokyo University of Science, 2641 Yamazaki, Noda, 278-8510, Japan.
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Yu J, Lee SH, Kim MK. Recent Updates to Clinical Practice Guidelines for Diabetes Mellitus. Endocrinol Metab (Seoul) 2022; 37:26-37. [PMID: 35255599 PMCID: PMC8901964 DOI: 10.3803/enm.2022.105] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 01/24/2022] [Accepted: 02/06/2022] [Indexed: 11/12/2022] Open
Abstract
Guidelines for the management of patients with diabetes have become an important part of clinical practice that improve the quality of care and help establish evidence-based medicine in this field. With rapidly accumulating evidence on various aspects of diabetes care, including landmark clinical trials of treatment agents and newer technologies, timely updates of the guidelines capture the most current state of the field and present a consensus. As a leading academic society, the Korean Diabetes Association publishes practice guidelines biennially and the American Diabetes Association does so annually. In this review, we summarize the key changes suggested in the most recent guidelines. Some of the important updates include treatment algorithms emphasizing comorbid conditions such as atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease in the selection of anti-diabetic agents; wider application of continuous glucose monitoring (CGM), insulin pump technologies and indices derived from CGM such as time in range; more active screening of subjects at high-risk of diabetes; and more detailed individualization in diabetes care. Although there are both similarities and differences among guidelines and some uncertainty remains, these updates provide a good approach for many clinical practitioners who are battling with diabetes.
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Affiliation(s)
- Jin Yu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Seung-Hwan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Mee Kyoung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
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Abstract
The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc22-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc22-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Lisco G, De Tullio A, Disoteo O, De Geronimo V, Piazzolla G, De Pergola G, Giagulli VA, Jirillo E, Guastamacchia E, Sabbà C, Triggiani V. Basal insulin intensification with GLP-1RA and dual GIP and GLP-1RA in patients with uncontrolled type 2 diabetes mellitus: A rapid review of randomized controlled trials and meta-analysis. Front Endocrinol (Lausanne) 2022; 13:920541. [PMID: 36157450 PMCID: PMC9494570 DOI: 10.3389/fendo.2022.920541] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 04/14/2022] [Accepted: 08/19/2022] [Indexed: 11/13/2022] Open
Abstract
Tirzepatide, a dual agonist of Glucose-Dependent Insulinotropic Polypeptide (GIP) and Glucagon-Like Peptide 1 (GLP-1) receptors, improved glucose control and reduced body weight in different therapeutic approaches. Herein, we overviewed the role of GIP and GLP-1 in the pathophysiology of type 2 diabetes and systematically reviewed the efficacy and safety of injectable incretin-based therapy added to basal insulin in light of the results of the SURPASS-5 trial. We identified eleven randomized clinical trials. GLP-1 receptor agonists (GLP-1RAs) or Tirzepatide added to basal insulin than rigorously titrated basal insulin significantly ameliorates glucose control (Δ HbA1c = -1%, 95% CI -1.25; -0.74, I2 94%; Δ FPG = -14.6 mg/dL, 95% CI -21.6-; -7.6, I2 90%; chance to achieve HbA1c <7% = RR 2.62, 95% CI 2.10; 3.26, I2 89%), reduces body weight (Δ = -3.95 kg, 95% CI -5.1, -2.79, I2 96%) without increasing the risk of hypoglycemia (RR = 1.01, 95% CI 0.86; 1.18, I2 7.7%). Tirzepatide provides an impressive weight loss exceeding that observed with GLP-1RAs. Injectable incretin-based therapy plus basal insulin remains a potent and safe therapeutic approach in uncontrolled type 2 diabetes patients previously treated with basal insulin alone. Tirzepatide is expected to ameliorate the management of "diabesity" in this usually difficult-to-treat cluster of patients.
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Affiliation(s)
- Giuseppe Lisco
- Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari “Aldo Moro”, School of Medicine, Policlinico, Bari, Italy
| | - Anna De Tullio
- Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari “Aldo Moro”, School of Medicine, Policlinico, Bari, Italy
| | - Olga Disoteo
- Diabetology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | | | - Giuseppina Piazzolla
- Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari “Aldo Moro”, School of Medicine, Policlinico, Bari, Italy
| | - Giovanni De Pergola
- National Institute of Gastroenterology, Saverio de Bellis, Research Hospital, Bari, Italy
| | - Vito Angelo Giagulli
- Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari “Aldo Moro”, School of Medicine, Policlinico, Bari, Italy
| | - Emilio Jirillo
- Department of Basic Medical Sciences, Neuroscience and Sensory Organs, School of Medicine, University of Bari, Bari, Italy
| | - Edoardo Guastamacchia
- Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari “Aldo Moro”, School of Medicine, Policlinico, Bari, Italy
| | - Carlo Sabbà
- Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari “Aldo Moro”, School of Medicine, Policlinico, Bari, Italy
| | - Vincenzo Triggiani
- Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari “Aldo Moro”, School of Medicine, Policlinico, Bari, Italy
- *Correspondence: Vincenzo Triggiani,
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Ramírez-Rincón A, Builes-Montaño CE, Hincapié-García JA, Blanco VM, Botero-Arango JF. Short-Term Effectiveness and Reduction in Insulin Requirements in Patients With Type 2 Diabetes Treated With IdegLira in a Real-World Setting. Front Endocrinol (Lausanne) 2022; 13:828607. [PMID: 35573995 PMCID: PMC9097264 DOI: 10.3389/fendo.2022.828607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 12/03/2021] [Accepted: 03/29/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) is a chronic, highly prevalent disease with a significant impact on health. Appropriate treatment requires effective and timely escalation to achieve metabolic control. To evaluate the effectiveness and safety of IDegLira on adults with T2DM previously treated with oral antidiabetics and/or insulin in a real-life setting. METHODS An observational study in a real-world setting was conducted. Patients were selected from the outpatient clinic of two centers dedicated to specialized diabetes care. Main outcomes were HbA1c, body weight, insulin dose changes, hypoglycemia, and other adverse events. RESULTS 67 T2DM patients treated with IDegLira were monitored between 3 and 7 months. At the end of foll ow-up, the median change in HbA1c was -1.05% (CI95% -1.45, -0.65), and a decrease in insulin requirement was also observed (mean difference -10 TDD units (CI95% - 17 to -2.5). No treatment discontinuation was reported, hypoglycemia events were reported in 3 patients at the end of follow-up versus 8 patients at baseline. CONCLUSIONS This real-life study shows the effectiveness in glycemic control of IDegLira use in T2DM patients who do not achieve goals with other therapies, with an adequate safety profile. The findings need to be confirmed with evaluation of therapeutic results in larger cohorts.
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Affiliation(s)
- Alex Ramírez-Rincón
- School of Medicine, Universidad Pontificia Bolivariana, Medellín, Colombia
- Endocrinology Department, Clínica Integral de Diabetes, Medellín, Colombia
- *Correspondence: Alex Ramírez-Rincón,
| | - Carlos E. Builes-Montaño
- School of Medicine, Universidad de Antioquia, Medellín, Colombia
- Endocrinology Department, Hospital Pablo Tobón Uribe, Medellín, Colombia
| | - Jaime A. Hincapié-García
- Clinical Pharmacology, Pharmaceutical Promotion and Prevention Group, Faculty of Pharmaceutical and Food Sciences, Universidad de Antioquia, Medellín, Colombia
| | - Victor M. Blanco
- School Medicine, Pontificia Universidad Bolivariana, Medellín, Colombia
| | - José F. Botero-Arango
- School of Medicine, Universidad Pontificia Bolivariana, Medellín, Colombia
- Endocrinology Department, Clínica Integral de Diabetes, Medellín, Colombia
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Pei Y, Agner BR, Luo B, Dong X, Li D, Liu J, Liu L, Liu M, Lu Y, Nishida T, Xu X, Mu Y. DUAL II China: Superior HbA1c reductions and weight loss with insulin degludec/liraglutide (IDegLira) versus insulin degludec in a randomized trial of Chinese people with type 2 diabetes inadequately controlled on basal insulin. Diabetes Obes Metab 2021; 23:2687-2696. [PMID: 34387411 PMCID: PMC9291809 DOI: 10.1111/dom.14522] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 05/12/2021] [Revised: 07/28/2021] [Accepted: 08/10/2021] [Indexed: 12/17/2022]
Abstract
AIM To assess the efficacy and safety of insulin degludec/liraglutide (IDegLira) versus insulin degludec (degludec) in Chinese people with type 2 diabetes (T2D) treated with basal insulin. MATERIALS AND METHODS In DUAL II China, a randomized, double-blinded, multicentre, treat-to-target trial, Chinese adults with T2D and HbA1c of 7.5% or more on basal insulin and metformin, with or without other oral antidiabetic drugs (OADs), were randomized 2:1 to 26 weeks of treatment with either IDegLira (max. dose 50 U degludec/1.8 mg liraglutide) or degludec (max. 50 U/day), respectively, combined with metformin. At 26 weeks, superiority of IDegLira over degludec was assessed for change in HbA1c (primary endpoint), and body weight and number of severe or blood glucose (BG)-confirmed hypoglycaemic episodes (confirmatory secondary endpoints). RESULTS Overall, 453 participants were randomized to IDegLira (n = 302) or degludec (n = 151). Superiority was confirmed for IDegLira over degludec in HbA1c change (-1.9% vs. -1.0%, respectively, estimated treatment difference [ETD] [95% confidence interval]: -0.92% [-1.09; -0.75], P < .0001), body weight change (-0.7 vs. +0.4 kg, respectively, ETD [95% CI]: -1.08 kg [-1.63; -0.52], P = .0002) and severe or BG-confirmed hypoglycaemia (estimated rate ratio [95% CI]: 0.53 [0.30; 0.94], P = .0297). The odds of achieving HbA1c less than 7.0% without hypoglycaemia and/or weight gain were greater with IDegLira than degludec (P < .0001 for all). Daily insulin dose at 26 weeks was lower for IDegLira (34.3 U) than degludec (37.4 U) (P = .0014). No unexpected safety signals were observed. CONCLUSIONS IDegLira may be an efficacious and well-tolerated treatment intensification option for Chinese people with T2D uncontrolled on basal insulin and OADs.
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Affiliation(s)
- Yu Pei
- Department of EndocrinologyChinese People's Liberation Army General HospitalBeijingChina
| | | | - Bin Luo
- Novo Nordisk China PharmaceuticalsBeijingChina
| | - Xiaolin Dong
- Department of EndocrinologyJinan Central Hospital, Shandong UniversityJinanChina
| | - Dongmei Li
- Department of EndocrinologyInner Mongolia People's HospitalHohhotChina
| | - Jun Liu
- Department of EndocrinologyFifth People's Hospital of ShanghaiShanghaiChina
| | - Lei Liu
- Novo Nordisk A/SSøborgDenmark
| | - Ming Liu
- Department of Endocrinology and MetabolismTianjin Medical University General HospitalTianjinChina
| | - Yibing Lu
- Department of EndocrinologyThe Second Affiliated Hospital of Nanjing Medical UniversityNanjingChina
| | | | - Xiangjin Xu
- Department of EndocrinologyFuzhou General HospitalFuzhouChina
| | - Yiming Mu
- Department of EndocrinologyChinese People's Liberation Army General HospitalBeijingChina
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Mehta R, Goldenberg R, Katselnik D, Kuritzky L. Practical guidance on the initiation, titration, and switching of basal insulins: a narrative review for primary care. Ann Med 2021; 53:998-1009. [PMID: 34165382 PMCID: PMC8231382 DOI: 10.1080/07853890.2021.1925148] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 12/16/2020] [Accepted: 04/28/2021] [Indexed: 01/22/2023] Open
Abstract
Many patients with type 2 diabetes will ultimately require the inclusion of basal insulin in their treatment regimen. Since most people with type 2 diabetes are managed in the community, it is important that primary care providers understand and correctly manage the initiation and titration of basal insulins, and help patients to self-manage insulin injections. Newer, long-acting basal insulins provide greater stability and flexibility than older preparations and improved delivery systems. Basal insulin is usually initiated at a conservative dose of 10 units/day or 0.1-0.2 units/kg/day, then titrated thereafter over several weeks or months, based on patients' self-measured fasting plasma glucose, to achieve an individualized target (usually 80-130 mg/dL). Through a shared decision-making process, confirmation of appropriate goals and titration methods should be established, including provisions for events that might alter scheduled titration (e.g. travel, dietary change, illness, hospitalization, etc.). Although switching between basal insulins is usually easily accomplished, pharmacokinetic and pharmacodynamic differences between formulations require clinicians to provide explicit guidance to patients. Basal insulin is effective long-term, but overbasalization (continuing to escalate dose without a meaningful reduction in fasting plasma glucose) should be avoided.Key messagesPrimary care providers often initiate basal insulin for people with type 2 diabetes.Basal insulin is recommended to be initiated at 10 units/day or 0.1-0.2 units/kg/day, and doses must be titrated to agreed fasting plasma glucose goals, usually 80-130 mg/dL. A simple rule is to gradually increase the initial dose by 1 unit per day (NPH, insulin detemir, and glargine 100 units/mL) or 2-4 units once or twice per week (NPH, insulin detemir, glargine 100 and 300 units/mL, and degludec) until FPG levels remain consistently within the target range. If warranted, switching between basal insulins can be done using simple regimens.The dose of basal insulin should be increased as required up to approximately 0.5-1.0 units/kg/day in some cases. Overbasalization (continuing to escalate dose without a meaningful reduction in fasting plasma glucose) is not recommended; rather re-evaluation of individual therapy, including consideration of more concentrated basal insulin preparations and/or short-acting prandial insulin as well as other glucose-lowering therapies, is suggested.
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Affiliation(s)
- Roopa Mehta
- National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico
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McCrimmon RJ, Falla E, Sha JZ, Alsaleh AJO, Lew E, Hudson R, Baxter M, Palmer K. Cost-Effectiveness of iGlarLixi in People with Type 2 Diabetes Mellitus Suboptimally Controlled on Basal Insulin Plus Metformin in the UK. Diabetes Ther 2021; 12:3217-3230. [PMID: 34714523 PMCID: PMC8586275 DOI: 10.1007/s13300-021-01159-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 08/04/2021] [Accepted: 09/18/2021] [Indexed: 01/28/2023] Open
Abstract
INTRODUCTION A cost-effectiveness analysis was conducted comparing a fixed-ratio combination (FRC) of insulin glargine 100 units/mL plus lixisenatide (iGlarLixi) versus the FRC of insulin degludec plus liraglutide (iDegLira) and the free-combination comparators insulin glargine plus dulaglutide (iGlar plus Dula) and basal insulin plus liraglutide (BI plus Lira). METHODS The IQVIA Core Diabetes Model was used to estimate lifetime costs and outcomes for a cohort of patients with type 2 diabetes mellitus (T2DM) from the UK healthcare perspective. Initial clinical data for iGlarLixi were based on the randomized, controlled LixiLan-L trial and the relative treatment effects for comparators were based on an indirect treatment comparison using data from the AWARD-9 (iGlar plus Dula), LIRA ADD2 BASAL (BI plus Lira), and DUAL V (iDegLira) trials. Costs were derived from publicly available sources. Lifetime costs (in British Pound Sterling [£]) and quality-adjusted life-years (QALYs) were predicted; net monetary benefit (NMB) for iGlarLixi versus comparators was derived using a willingness-to-pay threshold of £20,000. Extensive scenario and sensitivity analyses were conducted. RESULTS Estimated costs were lowest with iGlarLixi (£31,295) compared with iGlar plus Dula (£38,790), iDegLira (£40,179), and BI plus Lira (£42,467). Total QALYs gained were identical with iGlarLixi and iDegLira (8.438), and comparable with iGlar plus Dula (8.439) and BI plus Lira (8.466). NMB for iGlarLixi was positive versus all comparators (£10,603.86 vs. BI plus Lira; £7,466.24 vs. iGlar plus Dula; £8.874.11 vs. iDegLira). CONCLUSION In patients with T2DM with suboptimal glycemic control on basal insulin, iGlarLixi provides very similar outcomes and substantial cost savings, compared with other fixed and free combinations of insulins plus glucagon-like peptide-1 receptor agonists.
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Novodvorský P, Haluzík M. An update on the safety of insulin-GLP-1 receptor agonist combinations in type 2 diabetes mellitus. Expert Opin Drug Saf 2021; 21:349-361. [PMID: 34641742 DOI: 10.1080/14740338.2021.1978974] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 01/14/2023]
Abstract
INTRODUCTION Recent development of novel antidiabetic drugs with proven cardiovascular (CV) and renal benefit and positive effect on body weight enable to take a more complex approach toward the management of type 2 diabetes mellitus (T2DM). Fixed-ratio combinations of insulin-GLP-1 receptor agonist (FRC) utilize complementary mechanisms of action of their individual components and address multiple pathologies linked with T2DM at the same time. AREAS COVERED There are currently three FRCs on the market: iGlarLixi (glargine and lixisenatide in 2 different formulations) and IDegLira (degludec and liraglutide). We provide an up-to-date review on the rationale for the use of FRCs and their current position in the management of T2DM. We discuss the available evidence from randomized controlled trials, post hoc analyses, indirect comparative studies and real-world data on their effect on glycemic control, risk of hypoglycemia, body weight, CV safety, and their safety profile. EXPERT OPINION FRCs represent an efficacious option for treatment intensification from basal insulin or even the first insulin-based therapy in T2DM. Their excellent glucose-lowering efficacy is complemented with lower risk of hypoglycemia in comparison to basal insulin, neutral effect on body weight and the lower risk of gastrointestinal adverse effects in comparison to GLP-1 receptor agonists.
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Affiliation(s)
- Peter Novodvorský
- Diabetes Centre, Institute for Clinical and Experimental Medicine (Ikem), Prague, Czech Republic.,Department of Oncology & Metabolism, University of Sheffield, Sheffield, UK.,MUDr. Korecová Metabolické Centrum, Trenčín, Slovakia
| | - Martin Haluzík
- Diabetes Centre, Institute for Clinical and Experimental Medicine (Ikem), Prague, Czech Republic.,First Faculty of Medicine, Charles University, Prague, Czech Republic
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Komatsu M, Watada H, Kaneko S, Ross Agner BF, Nishida T, Kaku K. Efficacy and safety of the fixed-ratio combination of insulin degludec and liraglutide by baseline glycated hemoglobin, body mass index and age in Japanese individuals with type 2 diabetes: A subgroup analysis of two phase III trials. J Diabetes Investig 2021; 12:1610-1618. [PMID: 33595901 PMCID: PMC8409843 DOI: 10.1111/jdi.13525] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 10/26/2020] [Revised: 01/21/2021] [Accepted: 02/14/2021] [Indexed: 11/28/2022] Open
Abstract
AIMS/INTRODUCTION To assess efficacy and safety of insulin degludec/liraglutide (IDegLira) in Japanese participants with type 2 diabetes across different baseline characteristics. MATERIALS AND METHODS Data from two randomized controlled trials were used: DUAL I Japan (n = 819 insulin-naïve participants) and DUAL II Japan (n = 210 insulin-experienced participants). Outcomes were assessed according to baseline glycated hemoglobin ( HbA1c ; <8.0%, ≥8.0-<9.0%, ≥9.0%), body mass index (<25, ≥25-<30, ≥30 kg/m2 ) and age (<65, ≥65 years). RESULTS In DUAL I Japan, reductions in HbA1c with IDegLira versus degludec and liraglutide were observed across all subgroups (treatment differences: -0.48% to -0.72% vs degludec, -0.29% to -0.73% vs liraglutide). Results were similar with IDegLira versus degludec in DUAL II Japan (treatment differences: -0.82% to -1.61%). Treatment-by-subgroup interactions were significant for IDegLira versus liraglutide for baseline HbA1c and age in DUAL I Japan, and for IDegLira versus degludec for baseline HbA1c in DUAL II Japan. In DUAL I Japan, IDegLira was associated with less weight gain than degludec in most subgroups. In DUAL II Japan, IDegLira was associated with a small mean weight loss (except for baseline HbA1c ≥9.0%) versus a small gain for degludec (except for age ≥65 years subgroup); treatment-by-subgroup interactions were not significant. Total daily insulin dose was lower with IDegLira versus degludec across all categories, except for age >65 years in DUAL II Japan. CONCLUSIONS IDegLira reduced HbA1c in Japanese participants with type 2 diabetes across baseline HbA1c , body mass index and age categories, without unexpected safety issues.
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Affiliation(s)
- Mitsuhisa Komatsu
- Division of Diabetes, Endocrinology and MetabolismDepartment of Internal MedicineShinshu University School of MedicineNaganoJapan
| | - Hirotaka Watada
- Department of Metabolism and EndocrinologyJuntendo UniversityTokyoJapan
| | | | | | | | - Kohei Kaku
- Department of Internal MedicineKawasaki Medical SchoolKurashikiJapan
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Gomez‐Peralta F, Al‐Ozairi E, Jude EB, Li X, Rosenstock J. Titratable fixed-ratio combination of basal insulin plus a glucagon-like peptide-1 receptor agonist: A novel, simplified alternative to premix insulin for type 2 diabetes. Diabetes Obes Metab 2021; 23:1445-1452. [PMID: 33651460 PMCID: PMC8252507 DOI: 10.1111/dom.14365] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 12/04/2020] [Revised: 02/17/2021] [Accepted: 02/26/2021] [Indexed: 12/26/2022]
Abstract
Despite novel therapeutic options, many people with type 2 diabetes (T2D) do not achieve their HbA1c targets. Given the progressive nature of T2D, many individuals not controlled with oral therapy will require advancement to injectable therapy using either a glucagon-like peptide-1 receptor agonist (GLP-1 RA), recently recommended as a first option, or traditionally a basal insulin. However, premix insulins remain frequently used, either as initial injectable therapy or as intensification from basal insulin. Premix insulin injections can potentially provide significant glycaemic improvements to basal insulin but at the expense of increased hypoglycaemia and weight gain and the need for multiple daily doses, which may affect treatment adherence. Real-world evidence suggests that glycaemic control often remains suboptimal with premix insulins. Fixed-ratio combinations (FRCs) of basal insulin and GLP-1 RAs provide a novel alternative to premix insulin for therapy intensification. While no direct comparisons between premix insulins and FRCs are available, results from meta-analyses suggest that FRCs may offer better HbA1c reductions, a lower risk of hypoglycaemia and less weight gain compared with premix insulin in a simplified treatment regimen. A head-to-head trial of T2D treatment intensification with premix insulin and a FRC of basal insulin plus a GLP-1 RA is currently in progress, which should help to clarify the outcomes for each treatment option. This review discusses the unmet needs of people with T2D treated with premix insulin and provides evidence supporting FRCs of basal insulin and GLP-1 RAs as an alternative treatment option.
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Affiliation(s)
| | | | - Edward B. Jude
- Tameside and Glossop Integrated Care NHS Foundation TrustAshton‐under‐LyneUK
- University of ManchesterManchesterUK
| | - Xiaoying Li
- Department of Endocrinology, Zhongshan HospitalFudan UniversityShanghaiChina
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