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Cook AK, Behrend E. SGLT2 inhibitor use in the management of feline diabetes mellitus. J Vet Pharmacol Ther 2025; 48 Suppl 1:19-30. [PMID: 38954371 PMCID: PMC11736986 DOI: 10.1111/jvp.13466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 05/07/2024] [Accepted: 06/10/2024] [Indexed: 07/04/2024]
Abstract
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are routinely used in the management of human type 2 diabetes and have been shown to effectively mitigate hyperglycemia and reduce the risks of cardiovascular and renal compromise. Two SGLT2 inhibitors, namely bexagliflozin and velagliflozin, were recently FDA approved for the treatment of uncomplicated feline diabetes mellitus. These oral hypoglycemic agents are a suitable option for many newly diagnosed cats, with rapid improvements in glycemic control and clinical signs. Suitable candidates must have some residual β-cell function, as some endogenous insulin production is required to prevent ketosis. Appropriate patient selection and monitoring are necessary, and practitioners should be aware of serious complications such as euglycemic diabetic ketoacidosis.
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Affiliation(s)
- Audrey K. Cook
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical SciencesTexas A&M UniversityCollege StationTexasUSA
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Talebi SS, Rezaie S, Hajmiri MS, Zamanirafe M, Ranjbar A, Moridi H, Mirjalili M, Mehrpooya M. Comparison of the effects of empagliflozin and sitagliptin, as add-on to metformin, on serum levels of asprosin and metabolic parameters in patients with type 2 diabetes mellitus. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:9149-9165. [PMID: 38900252 DOI: 10.1007/s00210-024-03219-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 06/04/2024] [Indexed: 06/21/2024]
Abstract
The effect of sitagliptin and empagliflozin on serum levels of asprosin and metabolic parameters in patients with type 2 diabetes mellitus (T2DM) was assessed in a non-randomized, prospective observational study. Seventy-nine T2DM patients, without adequate glycemic control with metformin monotherapy, were included in the study. In addition to the ongoing metformin treatment, patients received sitagliptin 100 mg and empagliflozin 10 mg once daily for 12 weeks. Anthropometric parameters, lipid and glycemic profile, insulin resistance (homeostasis model assessment of insulin resistance index [HOMA-IR]), and asprosin serum levels were assessed at baseline and after 12 weeks of therapy. Both empagliflozin and sitagliptin treatments led to similar, significant improvement in fasting blood glucose (FBG) and hemoglobin A1C (HbA1C). Compared to baseline, triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) were improved with both treatments, but empagliflozin led to the more improvement. No significant change of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were observed in either group. Insulin resistance was significantly attenuated in both groups, but to a greater degree with empagliflozin treatment. The reduction in serum asprosin levels from baseline was significantly higher in patients taking empagliflozin compared to those receiving sitagliptin. Additionally, individuals on empagliflozin exhibited a more decrease in body mass index (BMI) and body weight compared to those on sitagliptin. According to our findings, the addition of empagliflozin to metformin appeared to offer greater benefits compared to the addition of sitagliptin in terms of decreasing asprosin levels and improving certain metabolic parameters in T2DM patients.
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Affiliation(s)
- Seyed Saman Talebi
- Department of Internal Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Shabnam Rezaie
- Department of Clinical Pharmacy, School of Pharmacy, Hamadan University of Medical Sciences, Shahid Fahmideh Ave, Hamadan, 6517838678, Iran
| | - Minoo Sadat Hajmiri
- Department of Internal Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Maryam Zamanirafe
- Medical Faculty, Hamadan University of Medical Science, Hamadan, Iran
| | - Akram Ranjbar
- Department of Pharmacology Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Heresh Moridi
- Department of Medical Laboratory Sciences, Faculty of Paramedical Sciences, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Mahtabalsadat Mirjalili
- Department of Clinical Pharmacy, School of Pharmacy, Yazd University of Medical Sciences, Yazd, Iran
| | - Maryam Mehrpooya
- Department of Clinical Pharmacy, School of Pharmacy, Hamadan University of Medical Sciences, Shahid Fahmideh Ave, Hamadan, 6517838678, Iran.
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Chai S, Niu Y, Liu F, Wu S, Yang Z, Sun F. Comparison of GLP-1 Receptor Agonists, SGLT-2 Inhibitors, and DPP-4 Inhibitors as an Add-On Drug to Insulin Combined With Oral Hypoglycemic Drugs: Umbrella Review. J Diabetes Res 2024; 2024:8145388. [PMID: 39072050 PMCID: PMC11283333 DOI: 10.1155/2024/8145388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2023] [Revised: 05/24/2024] [Accepted: 06/11/2024] [Indexed: 07/30/2024] Open
Abstract
Background: The objective was to evaluate the efficacy of the combination of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase-4 inhibitors (DPP-4i), and sodium-glucose cotransporter 2 inhibitor (SGLT-2i) in the treatment of Type 2 diabetes with poor efficacy of basic insulin and metformin/sulfonylurea by umbrella review. Materials and Methods: Forming the data of publication of each database through 13 September 2022, PubMed, EMBASE, and Cochrane Library were surveyed. Results: A total of seven meta-analyses were included in the umbrella review. The combination of GLP-1 RA (WMD -3.41 [-5.61, -1.21], p = 0.002), SGLT-2i (WMD -5.34 [-9.56, -1.13], p = 0.013), and DPP-4i (WMD -5.56 [-7.39, -3.73], p ≤ 0.001) can significantly reduce HbA1c levels, respectively. The combination of GLP-1 RA (WMD -1.55 [-2.92, -0.18], p = 0.027), SGLT-2i (WMD -2.96 [-6.68, 0.77], p = 0.12), and DPP-4i (WMD -2.05 [-2.82, -1.28], p ≤ 0.001) can significantly reduce fasting plasma glucose (FPG) levels, respectively. The combination of GLP-1 RA (WMD -3.24 [-5.14, -1.34], p < 0.001) can significantly reduce body weight of Type 2 diabetes mellitus (T2DM). The dose of basic insulin in diabetes patients after combined use of GLP-1 RA (WMD -2.74 [-4.26, -1.22], p ≤ 0.001) was significantly reduced. The combination use of GLP-1 RAs (OR 1.28 [1.05, 1.56], p = 0.017) increases the risk of hypoglycemia. Conclusions: The combination of GLP-1 RAs, DPP-4i, and SGLT-2i can effectively lower HbA1c and FPG in T2DM patients who have poor therapeutic effects on basic insulin combined with metformin/sulfonylureas, respectively. Compared to placebo, GLP-1 RAs can significantly reduce body weight and basic insulin dosage, while DPP-4i and SGLT-2i have a lower risk of hypoglycemia. Trial Registration: CRD42023410345.
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Affiliation(s)
- Sanbao Chai
- Department of Endocrinology and MetabolismPeking University International Hospital, Beijing 102206, China
| | - Yapin Niu
- Department of Epidemiology and BiostatisticsPeking University School of Public Health, Beijing 100083, China
| | - Fengqi Liu
- Department of Epidemiology and BiostatisticsPeking University School of Public Health, Beijing 100083, China
| | - Shanshan Wu
- National Clinical Research Center of Digestive DiseasesCapital Medical University Affiliated Beijing Friendship Hospital, Beijing 100050, China
| | - Zhirong Yang
- Shenzhen Institute of Advanced TechnologyChinese Academy of Sciences, Shenzhen 518055, China
| | - Feng Sun
- Department of Epidemiology and BiostatisticsPeking University School of Public Health, Beijing 100083, China
- Key Laboratory of Epidemiology of Major Disease (Peking University)Ministry of Education, Beijing 100191, China
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Preda A, Montecucco F, Carbone F, Camici GG, Lüscher TF, Kraler S, Liberale L. SGLT2 inhibitors: from glucose-lowering to cardiovascular benefits. Cardiovasc Res 2024; 120:443-460. [PMID: 38456601 PMCID: PMC12001887 DOI: 10.1093/cvr/cvae047] [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] [Scholar Register] [Received: 10/19/2023] [Revised: 01/03/2024] [Accepted: 02/05/2024] [Indexed: 03/09/2024] Open
Abstract
An increasing number of individuals are at high risk of type 2 diabetes (T2D) and its cardiovascular complications, including heart failure (HF), chronic kidney disease (CKD), and eventually premature death. The sodium-glucose co-transporter-2 (SGLT2) protein sits in the proximal tubule of human nephrons to regulate glucose reabsorption and its inhibition by gliflozins represents the cornerstone of contemporary T2D and HF management. Herein, we aim to provide an updated overview of the pleiotropy of gliflozins, provide mechanistic insights and delineate related cardiovascular (CV) benefits. By discussing contemporary evidence obtained in preclinical models and landmark randomized controlled trials, we move from bench to bedside across the broad spectrum of cardio- and cerebrovascular diseases. With landmark randomized controlled trials confirming a reduction in major adverse CV events (MACE; composite endpoint of CV death, non-fatal myocardial infarction, and non-fatal stroke), SGLT2 inhibitors strongly mitigate the risk for heart failure hospitalization in diabetics and non-diabetics alike while conferring renoprotection in specific patient populations. Along four major pathophysiological axes (i.e. at systemic, vascular, cardiac, and renal levels), we provide insights into the key mechanisms that may underlie their beneficial effects, including gliflozins' role in the modulation of inflammation, oxidative stress, cellular energy metabolism, and housekeeping mechanisms. We also discuss how this drug class controls hyperglycaemia, ketogenesis, natriuresis, and hyperuricaemia, collectively contributing to their pleiotropic effects. Finally, evolving data in the setting of cerebrovascular diseases and arrhythmias are presented and potential implications for future research and clinical practice are comprehensively reviewed.
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Affiliation(s)
- Alberto Preda
- Department of Clinical Cardiology, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy
| | - Fabrizio Montecucco
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
- IRCCS Ospedale Policlinico San Martino Genoa—Italian Cardiovascular Network, Genoa, Italy
| | - Federico Carbone
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
- IRCCS Ospedale Policlinico San Martino Genoa—Italian Cardiovascular Network, Genoa, Italy
| | - Giovanni G Camici
- Center for Molecular Cardiology, University of Zürich, Schlieren, Switzerland
- Department of Research and Education, University Hospital Zurich, Zurich, Switzerland
| | - Thomas F Lüscher
- Center for Molecular Cardiology, University of Zürich, Schlieren, Switzerland
- Royal Brompton and Harefield Hospitals and Imperial College and King’s College, London, United Kingdom
| | - Simon Kraler
- Center for Molecular Cardiology, University of Zürich, Schlieren, Switzerland
- Department of Internal Medicine, Cantonal Hospital Baden, Baden, Switzerland
| | - Luca Liberale
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
- IRCCS Ospedale Policlinico San Martino Genoa—Italian Cardiovascular Network, Genoa, Italy
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Zhang Q, Zhang Q, Yang L, Yang S, Lu Y. Renal, cardiovascular, and safety outcomes of adding sodium-glucose cotransporter-2 inhibitors to insulin therapy in patients with type-2 diabetes: a meta-analysis. Int Urol Nephrol 2024; 56:557-570. [PMID: 37515749 DOI: 10.1007/s11255-023-03719-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Accepted: 07/23/2023] [Indexed: 07/31/2023]
Abstract
AIMS To investigate the renal, cardiovascular, and safety outcomes when sodium-glucose cotransporter-2 inhibitors (SGLT2is) were added to insulin therapy in patients with type-2 diabetes mellitus (T2DM). MATERIALS AND METHODS We searched Embase, PubMed, and Cochrane libraries for reports published up to Feb 2023. Randomized controlled trials (RCTs) comparing SGLT2is and insulin combination therapy (SGLT2is + INS group) with insulin therapy alone (INS group) in T2DM were included. RESULTS Fourteen RCTs involving six thousand one hundred twenty subjects with durations of 12-104 weeks were included. Compared with the insulin group, the SGLT2is + INS group showed decreased glycosylated hemoglobin values and insulin dosages (P < 0.00001). Meanwhile, the SGLT2is + INS group had a reduced urinary albumin/creatinine ratio (UACR) by 25.42 mg/g and uric acid concentration (P = 0.030; P = 0.001, respectively) but the estimated glomerular filtration rate (eGFR) and renal-related adverse events were unaffected (P = 0.070; P = 0.880, respectively). Blood pressure and body weight were lower in the SGLT2is + INS group (P < 0.01). However, the risk of genital infection was bigger when SGLT2is were added to insulin therapy (P < 0.00001), but the risks of severe hypoglycemia or urinary tract infection were equal between the two groups (P > 0.05). CONCLUSION Adding SGLT2is to insulin therapy in T2DM patients showed better glucose control and decreased albuminuria, uric acid, blood pressure, and body weight without a reduction in the eGFR.
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Affiliation(s)
- Qian Zhang
- Department of Endocrinology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, 366 Taihu Road, Taizhou, 225300, China
| | - Qingqing Zhang
- Department of Endocrinology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, 366 Taihu Road, Taizhou, 225300, China
| | - Liu Yang
- Department of Endocrinology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, 366 Taihu Road, Taizhou, 225300, China
- Graduate School of Dalian Medical University, Dalian, 116044, Liaoning, China
| | - Shufang Yang
- Department of Endocrinology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, 366 Taihu Road, Taizhou, 225300, China
| | - Yu Lu
- Department of Endocrinology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, 366 Taihu Road, Taizhou, 225300, China.
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Lin C, Li ZL, Cai XL, Hu SY, Lv F, Yang WJ, Ji LN. Indirect comparison of efficacy and safety of chiglitazar and thiazolidinedione in patients with type 2 diabetes: A meta-analysis. World J Diabetes 2023; 14:1573-1584. [PMID: 37970134 PMCID: PMC10642417 DOI: 10.4239/wjd.v14.i10.1573] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 07/22/2023] [Accepted: 08/17/2023] [Indexed: 10/09/2023] Open
Abstract
BACKGROUND Chiglitazar is an emerging pan-agonist of all peroxisome proliferator activated receptors (PPAR)-α, δ and γ, and has therapeutic potential for type 2 diabetes (T2D). However, to date, no clinical studies or meta-analyses have compared the efficacy and safety of chiglitazar and traditional PPAR-γ agonist thiazolidinediones (TZDs). A meta-analysis concerning this topic is therefore required. AIM To compare the efficacy and safety of chiglitazar and TZD in patients with T2D. METHODS PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials, Reference Citation Analysis and Clinicaltrial.gov websites were searched from August 1994 to March 2022. Randomized controlled trials (RCTs) of chiglitazar or TZD vs placebo in patients with T2D were included. Indirect comparisons and sensitivity analyses were implemented to evaluate multiple efficacy and safety endpoints of interest. RESULTS We included 93 RCTs that compared TZD with placebo and one that compared chiglitazar with placebo. For efficacy endpoints, the augmented dose of chig-litazar resulted in greater reductions in hemoglobin (Hb)A1c [weighted mean difference (WMD) = -0.15%, 95% confidence interval (CI): -0.27 to -0.04%], triglycerides (WMD = -0.17 mmol/L, 95%CI: -0.24 to -0.11 mmol/L) and alanine aminotransferase (WMD = -5.25 U/L, 95%CI: -8.50 to -1.99 U/L), and a greater increase in homeostasis model assessment-β (HOMA-β) (WMD = 17.75, 95%CI: 10.73-24.77) when compared with TZD treatment. For safety endpoints, the risks of hypoglycemia, edema, bone fractures, upper respiratory tract infection, urinary tract infection, and weight gain were all comparable between the augmented dose of chiglitazar and TZD. In patients with baseline HbA1c ≥ 8.5%, body mass index ≥ 30 kg/m2 or diabetes duration < 10 years, the HbA1c reduction and HOMA-β increase were more conspicuous for the augmented dose of chiglitazar compared with TZD. CONCLUSION Augmented dose of chiglitazar, a pan-activator of PPARs, may serve as an antidiabetic agent with preferable glycemic and lipid control, better β-cell function preserving capacity, and does not increase the risk of safety concerns when compared with TZD.
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Affiliation(s)
- Chu Lin
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China
| | - Zong-Lin Li
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China
| | - Xiao-Ling Cai
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China
| | - Sui-Yuan Hu
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China
| | - Fang Lv
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China
| | - Wen-Jia Yang
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China
| | - Li-Nong Ji
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China
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Wu T, Wong CKH, Lui DTW, Wong SKH, Lam CLK, Chung MSH, McAllister DA, Welbourn R, Dixon JB. Bariatric surgery, novel glucose-lowering agents, and insulin for type 2 diabetes and obesity: Bayesian network meta-analysis of randomized controlled trials. BJS Open 2023; 7:zrad077. [PMID: 37542473 PMCID: PMC10404007 DOI: 10.1093/bjsopen/zrad077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 04/19/2023] [Accepted: 06/28/2023] [Indexed: 08/07/2023] Open
Abstract
BACKGROUND This network meta-analysis aimed to compare the effects of bariatric surgery, novel glucose-lowering agents (SGLT2i, GLP1RA, DPP4i), and insulin for patients with type 2 diabetes mellitus (T2DM) and obesity. METHODS Four databases were searched from inception to April 2023 to identify randomized controlled trials (RCTs) comparing bariatric surgery, SGLT2i, GLP1RA, DPP4i, insulin, and/or placebo/usual care among patients with T2DM and obesity in the achievement of HbA1c < 7.0 per cent within one year, and 12-month changes in HbA1c and body weight. RESULTS A total of 376 eligible RCTs (149 824 patients) were analysed. Bariatric surgery had significantly higher rates of achieving HbA1c < 7.0 per cent than SGLT2i (RR = 2.46, 95 per cent c.i. = 1.28, 4.92), DPP4i (RR = 2.59, 95 per cent c.i. = 1.36, 5.13), insulin (RR = 2.27, 95 per cent c.i. = 1.18, 4.58) and placebo/usual care (RR = 4.02, 95 per cent c.i. = 2.13, 7.93), but had no statistically significant difference from GLP1RA (RR = 1.73, 95 per cent c.i. = 0.91, 3.44), regardless of oral (RR = 1.33, 95 per cent c.i. = 0.66, 2.79) or injectable (RR = 1.75, 95 per cent c.i. = 0.92, 3.45) administration. Significantly more GLP1RA patients achieved HbA1c < 7.0 per cent than other non-surgical treatments. Bariatric surgery had the greatest reductions in HbA1c (∼1 per cent more) and body weight (∼15 kg more) at 12 months. Among novel glucose-lowering medications, GLP1RA was associated with greater reductions in HbA1c than SGLT2i (-0.39 per cent, 95 per cent c.i. = -0.55, -0.22) and DPP4i (-0.51 per cent, 95 per cent c.i. = -0.64, -0.39) at 12 months, while GLP1RA (-1.74 kg, 95 per cent c.i. = -2.48, -1.01) and SGLT2i (-2.23 kg, 95 per cent c.i. = -3.07, -1.39) showed greater reductions in body weight than DPP4i at 12 months. CONCLUSION Bariatric surgery showed superiority in glycaemic control and weight management compared to non-surgical approaches. GLP1RA administered by oral or injectable form demonstrated reduced HbA1c and body weight at 12 months, and was preferable over other non-surgical treatments among patients with T2DM and obesity. PROSPERO REGISTRATION NO CRD42020201507.
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Affiliation(s)
- Tingting Wu
- Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Carlos K H Wong
- Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Laboratory of Data Discovery for Health Limited (D24H), Hong Kong Science Park, New Territories, Hong Kong SAR, China
| | - David T W Lui
- Division of Endocrinology and Metabolism, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Simon K H Wong
- Division of Surgery, Chinese University of Hong Kong Medical Centre, Hong Kong SAR, China
- Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Cindy L K Lam
- Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Matthew S H Chung
- Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - David A McAllister
- Public Health, School of Health and Wellbeing, University of Glasgow, Glasgow, UK
| | - Richard Welbourn
- Department of Upper GI and Bariatric Surgery, Musgrove Park Hospital, Taunton, UK
| | - John B Dixon
- Iverson Health Innovation Research Institute, Swinburne University of Technology, Melbourne, VIC, Australia
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Kim J, Han K, Kim B, Baek KH, Song KH, Kim MK, Kwon HS. Sodium-glucose cotransporter 2 inhibitors for non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus: A nationwide propensity-score matched cohort study. Diabetes Res Clin Pract 2022; 194:110187. [PMID: 36442545 DOI: 10.1016/j.diabres.2022.110187] [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] [Scholar Register] [Received: 07/11/2022] [Revised: 11/02/2022] [Accepted: 11/21/2022] [Indexed: 11/27/2022]
Abstract
AIMS This study was to determine the association between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and nonalcoholic fatty liver disease (NAFLD) in type 2 diabetes. METHODS We used data from the Korean National Health Insurance Service from 2014 to 2017. New drug users were screened, dipeptidyl peptidase 4 inhibitors (DPP4i) were set as the active comparator, and the differences between the two groups were corrected through propensity score matching. NAFLD was evaluated by the fatty liver index (FLI), which was calculated using body mass index, waist circumference, triglycerides, and gamma glutamyl peptidase. RESULTS After 1:1 matching, 25,371 patients in each group who received medication for an average of 299 days were analyzed. Despite similar baseline FLI of each group, the FLI of the SGLT2i users was 44.4 ± 26.7 and the FLI of the DPP4i users was 48.9 ± 27.3 (P value < 0.001) after treatment. SGLT2i showed more significant decrements than DPP4i in all components of FLI. The more the adherence to the SGLT2i increased, the greater the decrease in FLI. CONCLUSIONS SGLT2i showed a significant reduction in FLI and its components. We suggest that SGLT2i may have beneficial effects in reducing the prevalence of NAFLD in type 2 diabetes.
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Affiliation(s)
- Jinyoung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
| | - Bongsung Kim
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
| | - Ki-Hyun Baek
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki-Ho Song
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of 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, Republic of Korea.
| | - Hyuk-Sang Kwon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
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Davis G, Bailey R, Calhoun P, Price D, Beck RW. Magnitude of Glycemic Improvement in Patients with Type 2 Diabetes Treated with Basal Insulin: Subgroup Analyses from the MOBILE Study. Diabetes Technol Ther 2022; 24:324-331. [PMID: 34962151 PMCID: PMC9127836 DOI: 10.1089/dia.2021.0489] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Objective: To determine if type 2 diabetes patients using basal insulin without prandial insulin with worse glycemic control at baseline would have the greatest benefit from using real-time continuous glucose monitoring (CGM). Methods: We conducted a post hoc analysis of the MOBILE Study, a multicenter trial examining the impact of CGM versus self-monitoring with a blood glucose meter (BGM) in patients with type 2 diabetes treated with basal insulin without prandial insulin. Participants were divided into subgroups based on baseline hemoglobin A1c (HbA1c) and baseline time-in-range 70-180 mg/dL (TIR). Change in TIR from baseline was calculated within each subgroup. Results: In subgroups based on baseline HbA1c, compared with the BGM group, the CGM group had 14% greater increase in TIR for participants with baseline HbA1c ≥8.5%, 14% greater increase for baseline HbA1c ≥9.0%, 22% greater increase for baseline HbA1c ≥9.5%, and 32% greater increase for baseline HbA1c ≥10.0% (P-value for interaction = 0.27). The time spent with glucose >250 mg/dL was significantly lower with CGM compared with BGM among participants with higher HbA1c values (P for interaction = 0.004). Results in subgroups based on baseline TIR paralleled the results in subgroups based on baseline HbA1c. Conclusion: While the benefit of CGM on TIR among patients with type 2 diabetes treated with basal insulin is apparent across the range of baseline glycemic control, the greatest impact of CGM is in those with the worst baseline glycemic control, particularly among those with HbA1c ≥10%. Clinical Trial Registration number: NCT03566693.
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Affiliation(s)
- Georgia Davis
- Emory University School of Medicine, Department of Medicine, Division of Endocrinology, Metabolism, and Lipids, Atlanta, GA
| | - Ryan Bailey
- Jaeb Center for Health Research, Tampa, Florida, USA
| | - Peter Calhoun
- Jaeb Center for Health Research, Tampa, Florida, USA
- Address correspondence to: Peter Calhoun, PhD, Jaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa, FL 33647, USA
| | | | - Roy W. Beck
- Jaeb Center for Health Research, Tampa, Florida, USA
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10
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Salvatore T, Galiero R, Caturano A, Rinaldi L, Di Martino A, Albanese G, Di Salvo J, Epifani R, Marfella R, Docimo G, Lettieri M, Sardu C, Sasso FC. An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors. Int J Mol Sci 2022; 23:3651. [PMID: 35409011 PMCID: PMC8998569 DOI: 10.3390/ijms23073651] [Citation(s) in RCA: 115] [Impact Index Per Article: 38.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/17/2022] [Accepted: 03/24/2022] [Indexed: 02/04/2023] Open
Abstract
Sodium-glucose co-transporter 2 (SGLT2) inhibitors block glucose reabsorption in the renal proximal tubule, an insulin-independent mechanism that plays a critical role in glycemic regulation in diabetes. In addition to their glucose-lowering effects, SGLT2 inhibitors prevent both renal damage and the onset of chronic kidney disease and cardiovascular events, in particular heart failure with both reduced and preserved ejection fraction. These unexpected benefits prompted changes in treatment guidelines and scientific interest in the underlying mechanisms. Aside from the target effects of SGLT2 inhibition, a wide spectrum of beneficial actions is described for the kidney and the heart, even though the cardiac tissue does not express SGLT2 channels. Correction of cardiorenal risk factors, metabolic adjustments ameliorating myocardial substrate utilization, and optimization of ventricular loading conditions through effects on diuresis, natriuresis, and vascular function appear to be the main underlying mechanisms for the observed cardiorenal protection. Additional clinical advantages associated with using SGLT2 inhibitors are antifibrotic effects due to correction of inflammation and oxidative stress, modulation of mitochondrial function, and autophagy. Much research is required to understand the numerous and complex pathways involved in SGLT2 inhibition. This review summarizes the current known mechanisms of SGLT2-mediated cardiorenal protection.
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Affiliation(s)
- Teresa Salvatore
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via De Crecchio 7, 80138 Naples, Italy
| | - Raffaele Galiero
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138 Naples, Italy
| | - Alfredo Caturano
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138 Naples, Italy
| | - Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138 Naples, Italy
| | - Anna Di Martino
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138 Naples, Italy
| | - Gaetana Albanese
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138 Naples, Italy
| | - Jessica Di Salvo
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138 Naples, Italy
| | - Raffaella Epifani
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138 Naples, Italy
| | - Raffaele Marfella
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138 Naples, Italy
- Mediterrannea Cardiocentro, 80122 Napoli, Italy
| | - Giovanni Docimo
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138 Naples, Italy
| | - Miriam Lettieri
- Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, 3.31 Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, UK
| | - Celestino Sardu
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138 Naples, Italy
| | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138 Naples, Italy
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11
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Lee YT, Hsu CN, Fu CM, Wang SW, Huang CC, Li LC. Comparison of Adverse Kidney Outcomes With Empagliflozin and Linagliptin Use in Patients With Type 2 Diabetic Patients in a Real-World Setting. Front Pharmacol 2022; 12:781379. [PMID: 34992535 PMCID: PMC8724779 DOI: 10.3389/fphar.2021.781379] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 12/02/2021] [Indexed: 12/15/2022] Open
Abstract
Background: To compare the effects of empagliflozin and linagliptin use on kidney outcomes of type 2 diabetes mellitus (T2DM) patients in a real-world setting. Methods: The study involved a propensity score-matched cohort comprising new users of empagliflozin or linagliptin with T2DM between January 1, 2013 and December 31, 2018 from a large healthcare delivery system in Taiwan. Clinical outcomes assessed: acute kidney injury (AKI), post-AKI dialysis, and mortality. Cox proportional hazard model was used to estimate the relative risk of empagliflozin or linagliptin use; a linear mixed model was used to compare the average change in estimated glomerular filtration rate (eGFR) over time. Results: Of the 7,042 individuals, 67 of 3,521 (1.9%) in the empagliflozin group and 144 of 3,521 (4.1%) in the linagliptin group developed AKI during the 2 years follow-up. Patients in the empagliflozin group were at a 40% lower risk of developing AKI compared to those in the linagliptin group (adjusted hazard ratio [aHR], 0.60; 95% confidence interval [CI], 0.45-0.82, p = 0.001). Stratified analysis showed that empagliflozin users ≥65 years of age (aHR, 0.70; 95% CI, 0.43-1.13, p = 0.148), or with a baseline eGFR <60 ml/min/1.73 m2 (aHR, 0.97; 95% CI, 0.57-1.65, p = 0.899), or with a baseline glycohemoglobin ≦7% (aHR, 1.01; 95% CI, 0.51-2.00, p =0.973) experienced attenuated benefits with respect to AKI risk. A smaller decline in eGFR was observed in empagliflozin users compared to linagliptin users regardless of AKI occurrence (adjusted β = 1.51; 95% CI, 0.30-2.72 ml/min/1.73 m2, p = 0.014). Conclusion: Empagliflozin users were at a lower risk of developing AKI and exhibited a smaller eGFR decline than linagliptin users. Thus, empagliflozin may be a safer alternative to linagliptin for T2DM patients.
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Affiliation(s)
- Yueh-Ting Lee
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chien-Ning Hsu
- Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.,School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Ming Fu
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Shih-Wei Wang
- Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chiang-Chi Huang
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Lung-Chih Li
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.,Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
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12
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Scheen AJ. Efficacy / safety balance of DPP-4 inhibitors versus SGLT2 inhibitors in elderly patients with type 2 diabetes. DIABETES & METABOLISM 2021; 47:101275. [PMID: 34481962 DOI: 10.1016/j.diabet.2021.101275] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 08/07/2021] [Indexed: 12/14/2022]
Abstract
Dipeptidyl peptidase-4 inhibitors (DPP-4is) and sodium-glucose cotransporter type 2 inhibitors (SGLT2is) offer new options for the oral management of type 2 diabetes mellitus (T2DM), with the advantage in the elderly population to be devoid of a high risk of hypoglycaemia. SGLT2is have also shown benefits regarding cardiovascular (heart failure) and renal protection, including in patients with T2DM aged ≥ 65 years while DPP-4is have only proved cardiovascular and renal safety without superiority compared with placebo. The glucose-lowering efficacy of the two pharmacological classes is almost similar including in older patients with T2DM. However, the tolerance and safety profile may be highly different and overall more favourable with DPP-4is than with SGLT2is. Some adverse events have been reported with SGLT2is which may be more prevalent or severe in older patients than in younger patients. The present comprehensive review focuses on the benefit/risk balance in the elderly population with T2DM by comparing the profile of DPP-4is and SGLT2is regarding the following potential issues: metabolic disorders (hypoglycaemia and diabetic ketoacidosis); cardiac and vascular issues (atheromatous cardiovascular disease, heart failure, volume reduction hypotension, and lower limb amputations); renal endpoints including acute renal injury; risk of infections; digestive disorders; bone and skin adverse events; and cancer risk. Both DPP-4is and SGLT2is have their own advantages and disadvantages. Personalised treatment is recommended based upon the efficacy/safety profile of each drug class and individual patient characteristics that may be markedly different among the heterogeneous population of older individuals with T2DM.
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Affiliation(s)
- André J Scheen
- Division of Clinical Pharmacology, Centre for Interdisciplinary Research on Medicines (CIRM), University of Liège, Liège, Belgium; Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Liège, Liège, Belgium.
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13
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Strain WD, Down S, Brown P, Puttanna A, Sinclair A. Diabetes and Frailty: An Expert Consensus Statement on the Management of Older Adults with Type 2 Diabetes. Diabetes Ther 2021; 12:1227-1247. [PMID: 33830409 PMCID: PMC8099963 DOI: 10.1007/s13300-021-01035-9] [Citation(s) in RCA: 86] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 02/13/2021] [Indexed: 02/08/2023] Open
Abstract
Prognosis and appropriate treatment goals for older adults with diabetes vary greatly according to frailty. It is now recognised that changes may be needed to diabetes management in some older people. Whilst there is clear guidance on the evaluation of frailty and subsequent target setting for people living with frailty, there remains a lack of formal guidance for healthcare professionals in how to achieve these targets. The management of older adults with type 2 diabetes is complicated by comorbidities, shortened life expectancy and exaggerated consequences of adverse effects from treatment. In particular, older adults are more prone to hypoglycaemia and are more vulnerable to its consequences, including falls, fractures, hospitalisation, cardiovascular events and all-cause mortality. Thus, assessment of frailty should be a routine component of a diabetes review for all older adults, and glycaemic targets and therapeutic choices should be modified accordingly. Evidence suggests that over-treatment of older adults with type 2 diabetes is common, with many having had their regimens intensified over preceding years when they were in better health, or during more recent acute hospital admissions when their blood glucose levels might have been atypically high, and nutritional intake may vary. In addition, assistance in taking medications, as often occurs in later life following implementation of community care strategies or admittance to a care home, may dramatically improve treatment adherence, leading to a fall in glycated haemoglobin (HbA1c) levels. As a person with diabetes gets older, simplification, switching or de-escalation of the therapeutic regimen may be necessary, depending on their level of frailty and HbA1c levels. Consideration should be given, in particular, to de-escalation of therapies that may induce hypoglycaemia, such as sulphonylureas and shorter-acting insulins. We discuss the use of available glucose-lowering therapies in older adults and recommend simple glycaemic management algorithms according to their level of frailty.
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Affiliation(s)
- W David Strain
- University of Exeter Medical School, and Royal Devon and Exeter Hospital, Exeter, UK.
| | - Su Down
- Somerset Foundation Trust, Somerset, UK
| | | | | | - Alan Sinclair
- The Foundation for Diabetes Research in Older People (fDROP) and King's College, London, UK
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14
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Scheen AJ. Careful use to minimize adverse events of oral antidiabetic medications in the elderly. Expert Opin Pharmacother 2021; 22:2149-2165. [PMID: 33823723 DOI: 10.1080/14656566.2021.1912735] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION An increasing number of older patients has type 2 diabetes treated with different oral antidiabetic agents whose safety may raise concern considering some particularities of a heterogeneous elderly population. AREAS COVERED This article discusses some characteristics of older patients that could increase the risk of adverse events, with a focus on hypoglycemia. It describes the most frequent and/or severe complications reported in the elderly in both randomized controlled trials and observational studies with metformin, sulfonylureas, meglitinides, alpha-glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase-4 inhibitors (gliptins) and sodium-glucose cotransporter type 2 inhibitors (gliflozins). EXPERT OPINION Old patients may present comorbidities (renal impairment, vascular disease, heart failure, risk of dehydration, osteoporosis, cognitive dysfunction) that could increase the risk of severe adverse events. Sulfonylureas (and meglitinides) induce hypoglycemia, which may be associated with falls/fractures and cardiovascular events. Medications lacking hypoglycemia should be preferred. Gliptins appear to have the best tolerance/safety profile whereas gliflozins exert a cardiorenal protection. However, data are lacking in very old or frailty old patients so that caution and appropriate supervision of such patients are required. Taking advantage of a large choice of pharmacotherapies, personalized treatment is recommended based upon both drug safety profiles and old patient individual characteristics.
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Affiliation(s)
- André J Scheen
- Division of Clinical Pharmacology, Centre for Interdisciplinary Research on Medicines (CIRM), University of Liège, Liège, Belgium.,Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Liège, Liège, Belgium
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15
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Guo S, Yan T, Shi L, Liu A, Zhang T, Xu Y, Jiang W, Yang Q, Yang L, Liu L, Zhao R, Zhang S. Matrine, as a CaSR agonist promotes intestinal GLP-1 secretion and improves insulin resistance in diabetes mellitus. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 84:153507. [PMID: 33636577 DOI: 10.1016/j.phymed.2021.153507] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 02/02/2021] [Accepted: 02/08/2021] [Indexed: 06/12/2023]
Abstract
BACKGROUND Matrine (Mat), a bitter tastes compounds of derived from leguminosae such as Sophora flavescens and S. subprostrata, commonly used to improve obesity and diabetes. PURPOSE Our study to demonstrate bitter substances can stimulate the Bitter taste receptors (TAS2Rs) or Calcium-sensing receptor (CaSR) to stimulate the secretion of GLP-1 to promote blood glucose regulation. METHODS The diabetic mice and intestinal secretory cell model were established to evaluate the Mat on glucose metabolism, intestinal insulin secretion and GLP-1 secretion related substances. To clarify the mechanism of Mat in regulating GLP-1 secretion by immunofluorescence, calcium labeling, siRNA, and molecular docking. RESULTS The results showed that Mat could significantly improve glucose metabolism and increased insulin and GLP-1 secretion in diabetic mice and increased trisphosphate inositol (IP3) levels by affecting the expression of phospholipase C β2 (PLCβ2) and promote an increase in intracellular Ca2+ levels in STC-1 cells to subsequently stimulate the secretion of GLP-1. Knockdown of the bitter taste receptors mTas2r108, mTas2r137, and mTas2r138 in STC-1 cells by siRNA did could not affect the role of Mat in regulating GLP-1. However, the secretion of GLP-1 by Mat could be significantly inhibited by administration of a CaSR inhibitor or siRNA CaSR. Molecular docking analysis showed that Mat could embed CaSR protein and bind to the original ligand of the egg white at the same amino acid site to play the role of an agonist. CONCLUSION Matrine is a typical bitter alkaloid could be used as an agonist of CaSR to stimulate the secretion of GLP-1 in the intestine, and it may be used as a potential drug for diabetes treatment.
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Affiliation(s)
- Shun Guo
- Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, Xi'an, 710038, PR China
| | - Tao Yan
- Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, Xi'an, 710038, PR China
| | - Lei Shi
- Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, Xi'an, 710038, PR China
| | - An Liu
- Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, Xi'an, 710038, PR China
| | - Tian Zhang
- Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, Xi'an, 710038, PR China
| | - Yuan Xu
- Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, Xi'an, 710038, PR China
| | - Wei Jiang
- Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, Xi'an, 710038, PR China
| | - Qi Yang
- Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, Xi'an, 710038, PR China
| | - Le Yang
- Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, Xi'an, 710038, PR China
| | - Linna Liu
- Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, Xi'an, 710038, PR China..
| | - Rong Zhao
- Department of Cardiovascular Surgery, The First Affiliated Hospital of Air Force Medical University, Xi'an 710032, PR China..
| | - Song Zhang
- Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, Xi'an, 710038, PR China..
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16
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Zhou JH, Wu B, Wang WX, Lei F, Cheng X, Qin JJ, Cai JJ, Zhang XJ, Zhou F, Liu YM, Li HM, Zhu LH, She ZG, Zhang X, Yang J, Li HL. No significant association between dipeptidyl peptidase-4 inhibitors and adverse outcomes of COVID-19. World J Clin Cases 2020; 8:5576-5588. [PMID: 33344548 PMCID: PMC7716296 DOI: 10.12998/wjcc.v8.i22.5576] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 08/20/2020] [Accepted: 09/25/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Dipeptidyl peptidase-4 (DPP4) is commonly targeted to achieve glycemic control and has potent anti-inflammatory and immunoregulatory effects. Recent structural analyses indicated a potential tight interaction between DPP4 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raising a promising hypothesis that DPP4 inhibitor (DPP4i) drugs might be an optimal strategy for treating coronavirus disease 2019 (COVID-19) among patients with diabetes. However, there has been no direct clinical evidence illuminating the associations between DPP4i use and COVID-19 outcomes.
AIM To illuminate the associations between DPP4i usage and the adverse outcomes of COVID-19.
METHODS We conducted a multicenter, retrospective analysis including 2563 patients with type 2 diabetes who were hospitalized due to COVID-19 at 16 hospitals in Hubei Province, China. After excluding ineligible individuals, 142 patients who received DPP4i drugs and 1115 patients who received non-DPP4i oral anti-diabetic drugs were included in the subsequent analysis. We performed a strict propensity score matching (PSM) analysis where age, sex, comorbidities, number of oral hypoglycemic agents, heart rate, blood pressure, pulse oxygen saturation (SpO2) < 95%, CT diagnosed bilateral lung lesions, laboratory indicators, and proportion of insulin usage were matched. Finally, 111 participants treated with DPP4i drugs were successfully matched to 333 non-DPP4i users. Then, a linear logistic model and mixed-effect Cox model were applied to analyze the associations between in-hospital DPP4i use and adverse outcomes of COVID-19.
RESULTS After rigorous matching and further adjustments for imbalanced variables in the linear logistic model and Cox adjusted model, we found that there was no significant association between in-hospital DPP4i use (DPP4i group) and 28-d all-cause mortality (adjusted hazard ratio = 0.44, 95%CI: 0.09-2.11, P = 0.31). Likewise, the incidences and risks of secondary outcomes, including septic shock, acute respiratory distress syndrome, or acute organ (kidney, liver, and cardiac) injuries, were also comparable between the DPP4i and non-DPP4i groups. The performance of DPP4i agents in achieving glucose control (e.g., the median level of fasting blood glucose and random blood glucose) and inflammatory regulation was approximately equivalent in the DPP4i and non-DPP4i groups. Furthermore, we did not observe substantial side effects such as uncontrolled glycemia or acidosis due to DPP4i application relative to the use of non-DPP4i agents in the study cohort.
CONCLUSION Our findings demonstrated that DPP4i use is not significantly associated with poor outcomes of COVID-19 or other adverse effects of anti-diabetic treatment. The data support the continuation of DPP4i agents for diabetes management in the setting of COVID-19.
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Affiliation(s)
- Jiang-Hua Zhou
- Department of Cardiology, Renmin Hospital of Wuhan University, Basic Medical School, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Bin Wu
- Department of Cardiology, Renmin Hospital of Wuhan University, Basic Medical School, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Wen-Xin Wang
- Department of Cardiology, Renmin Hospital of Wuhan University, Basic Medical School, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Fang Lei
- Basic Medical School, Institute of Model Animal, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Xu Cheng
- Department of Cardiology, Renmin Hospital of Wuhan University, Basic Medical School, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Juan-Juan Qin
- Department of Cardiology, Renmin Hospital of Wuhan University, Basic Medical School, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Jing-Jing Cai
- Department of Cardiology, the 3rd Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
| | - Xiao-Jing Zhang
- Basic Medical School, Institute of Model Animal, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Feng Zhou
- Medical Science Research Center, Zhongnan Hospital of Wuhan University, Institute of Model Animal, Wuhan University, Wuhan 430072, Hubei Province, China
| | - Ye-Mao Liu
- Department of Cardiology, Renmin Hospital of Wuhan University, Basic Medical School, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Hao-Miao Li
- Department of Cardiology, Renmin Hospital of Wuhan University, Basic Medical School, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Li-Hua Zhu
- Department of Cardiology, Renmin Hospital of Wuhan University; Institute of Model Animal of Wuhan University, Wuhan 430071, Hubei Province, China
| | - Zhi-Gang She
- Department of Cardiology, Renmin Hospital of Wuhan University; Institute of Model Animal of Wuhan University, Wuhan 430071, Hubei Province, China
| | - Xin Zhang
- Institute of Model Animal, Wuhan University, Department of Gastroenterology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan 430072, Hubei Province, China
| | - Juan Yang
- Department of Cardiology, Renmin Hospital of Wuhan University; Institute of Model Animal of Wuhan University, Wuhan 430071, Hubei Province, China
| | - Hong-Liang Li
- Department of Cardiology, Renmin Hospital of Wuhan University; Institute of Model Animal of Wuhan University, Wuhan 430071, Hubei Province, China
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Cowart K. Overbasalization: Addressing Hesitancy in Treatment Intensification Beyond Basal Insulin. Clin Diabetes 2020; 38:304-310. [PMID: 32699482 PMCID: PMC7364465 DOI: 10.2337/cd19-0061] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- Kevin Cowart
- Department of Pharmacotherapeutics & Clinical Research, Taneja College of Pharmacy and Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL
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18
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Abstract
BACKGROUND Since the discovery of insulin, it was the only drug available for the treatment of diabetes until the development of sulfonylureas and biguanides 50 years later. But even with the availability of oral glucose-lowering drugs, insulin supplementation was often needed to achieve good glucose control in type 2 diabetes. Insulin NPH became the basal insulin therapy of choice and adding NPH to metformin and/or sulfonylureas became the standard of care until basal insulin analogs were developed and new glucose-lowering drugs became available. AREAS OF UNCERTAINTY The advantages in cost-benefit of insulin analogs and their combination with new glucose-lowering drugs are still a matter of debate. There is no general agreement on how to avoid inertia by prescribing insulin therapy in type 2 diabetes when really needed, as reflected by the diversity of recommendations in the current clinical practice guidelines. DATA SOURCES When necessary for this review, a systematic search of the evidence was done in PubMed and Cochrane databases. THERAPEUTIC ADVANCES Adding new oral glucose-lowering drugs to insulin such as DPP-4 inhibitors lead to a modest HbA1c reduction without weight gain and no increase in hypoglycemia. When SGLT-2 inhibitors are added instead, there is a slightly higher HbA1c reduction, but with body weight and blood pressure reduction. The downside is the increase in genital tract infections. GLP-1 receptor agonists have become the best alternative when basal insulin fails, particularly using fixed ratio combinations. Rapid-acting insulins via the inhaled route may also become an alternative for insulin supplementation and/or intensification. "Smart insulins" are under investigation and may become available for clinical use in the near future. CONCLUSIONS Aggressive weight loss strategies together with the new glucose-lowering drugs which do not cause hypoglycemia nor weight gain should limit the number of patients with type 2 diabetes needing insulin. Nevertheless, because of therapeutic inertia and the progressive nature of the disease, many need at least a basal insulin supplementation and insulin analogs are the best choice as they become more affordable. Fixed ratio combinations with GLP1 receptor agonists are a good choice for intensification of insulin therapy.
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19
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Yang Y, Zhao C, Ye Y, Yu M, Qu X. Prospect of Sodium-Glucose Co-transporter 2 Inhibitors Combined With Insulin for the Treatment of Type 2 Diabetes. Front Endocrinol (Lausanne) 2020; 11:190. [PMID: 32351447 PMCID: PMC7174744 DOI: 10.3389/fendo.2020.00190] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Accepted: 03/17/2020] [Indexed: 12/25/2022] Open
Abstract
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new family of antidiabetic drugs that reduce blood glucose independent of insulin. In this review, we present the advantages and adverse effects of SGLT2 inhibitors plus insulin therapy as a treatment regimen for patients with type 2 diabetes (T2D). Compared with placebo, SGLT2 inhibitors plus insulin therapy could significantly decrease fasting blood glucose and HbA1c, thereby reducing the daily required dose of insulin. A reduction in body weight and improvements in insulin resistance and β-cell function have also been widely reported with this therapy, and other potential advantages, including the reduction in blood pressure, adverse cardiovascular outcomes, and visceral adipose tissue volume, have been revealed. SGLT2 inhibitors cause a greater reduction than dipeptidyl peptidase-4 (DPP-4) inhibitors in body weight and the risk of cardiovascular disease. Furthermore, compared with glucagon-like peptide-1 (GLP-1) agonists, SGLT2 inhibitors reduce blood pressure, and heart failure. As this therapy is an oral preparation, an improvement in patient compliance is also achieved. Despite these advantages, however, combination therapy with SGLT2 inhibitors and insulin has several risks. Although no difference has been found in the incidence of hypoglycemic events and urinary tract infection between the administration of this combination and that of placebo, the risk of genital tract infections was reported to increase with the combination therapy. Additionally, bone adverse effects, euglycemic diabetic ketoacidosis, and volume depletion-and osmotic diuresis-related adverse effects have been observed. Altogether, we could conclude that SGLT2 inhibitors plus insulin therapy is an efficient treatment option for patients with T2D, especially those requiring high daily insulin doses and those with insulin resistance, obesity, and a high risk of cardiovascular events. However, careful monitoring of the adverse effects of this combination is also warranted.
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Affiliation(s)
- Yinqiu Yang
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chenhe Zhao
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yangli Ye
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Mingxiang Yu
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, China
- *Correspondence: Mingxiang Yu
| | - Xinhua Qu
- Department of Bone and Joint Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Xinhua Qu
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20
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Les inhibiteurs des SGLT2 : traitement anti diabétiques et/ou de la prévention cardiovasculaire et/ou protection rénale ? Place au débat. ARCHIVES OF CARDIOVASCULAR DISEASES SUPPLEMENTS 2019. [DOI: 10.1016/s1878-6480(19)30962-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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21
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Shen Y, Dai Y, Wang XQ, Zhang RY, Lu L, Ding FH, Shen WF. Searching for optimal blood pressure targets in type 2 diabetic patients with coronary artery disease. Cardiovasc Diabetol 2019; 18:160. [PMID: 31733658 PMCID: PMC6858977 DOI: 10.1186/s12933-019-0959-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 10/31/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Controversies exist regarding the optimal blood pressure (BP) level that is safe and provides cardiovascular protection in patients with type 2 diabetes mellitus (T2DM) and coexistent coronary artery disease. Several new glucose-lowering agents have been found to lower BP as well, making the interaction between BP and T2DM even more complex. METHODS With the reference to recent literature, this review article describes the potential mechanisms of increased risk of hypertension in T2DM and outlines the possible optimal BP levels based upon recommendations on the management of hypertension by the current guidelines, in combination with our research findings, for type 2 diabetic patients with coronary artery disease. RESULTS The development of hypertension in T2DM involves multiple processes, including enhanced sympathetic output, inappropriate activation of renin-angiotensin- aldosterone system, endothelial dysfunction induced through insulin resistance, and abnormal sodium handling by the kidney. Both AGE-RAGE axis and adipokine dysregulation activate intracellular signaling pathways, increase oxidative stress, and aggravate vascular inflammation. Pancreatic β-cell specific microRNAs are implicated in gene expression and diabetic complications. Non-pharmacological intervention with lifestyle changes improves BP control, and anti-hypertensive medications with ACEI/ARB, calcium antagonists, β-blockers, diuretics and new hypoglycemic agent SGLT2 inhibitors are effective to decrease mortality and prevent major adverse cardiovascular events. For hypertensive patients with T2DM and stable coronary artery disease, control of BP < 130/80 mmHg but not < 120/70 mmHg is reasonable, whereas for those with chronic total occlusion or acute coronary syndromes, an ideal BP target may be somewhat higher (< 140/90 mmHg). Caution is advised with aggressive lowering of diastolic BP to a critical threshold (< 60 mmHg). CONCLUSIONS Hypertension and T2DM share certain similar aspects of pathophysiology, and BP control should be individualized to minimize adverse events and maximize benefits especially for patients with T2DM and coronary artery disease.
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Affiliation(s)
- Ying Shen
- Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China
| | - Yang Dai
- Institute of Cardiovascular Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China
| | - Xiao Qun Wang
- Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China
| | - Rui Yan Zhang
- Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China
| | - Lin Lu
- Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China.,Institute of Cardiovascular Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China
| | - Feng Hua Ding
- Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China.
| | - Wei Feng Shen
- Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China. .,Institute of Cardiovascular Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China.
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22
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Chawla R, Makkar BM, Aggarwal S, Bajaj S, Das AK, Ghosh S, Gupta A, Gupta S, Jaggi S, Jana J, Keswadev J, Kalra S, Keswani P, Kumar V, Maheshwari A, Moses A, Nawal CL, Panda J, Panikar V, Ramchandani GD, Rao PV, Saboo B, Sahay R, Setty KR, Viswanathan V, Aravind SR, Banarjee S, Bhansali A, Chandalia HB, Das S, Gupta OP, Joshi S, Kumar A, Kumar KM, Madhu SV, Mittal A, Mohan V, Munichhoodappa C, Ramachandran A, Sahay BK, Sai J, Seshiah V, Zargar AH. RSSDI consensus recommendations on insulin therapy in the management of diabetes. Int J Diabetes Dev Ctries 2019. [DOI: 10.1007/s13410-019-00783-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
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23
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Zhou FL, Watada H, Tajima Y, Berthelot M, Kang D, Esnault C, Shuto Y, Maegawa H, Koya D. Identification of subgroups of patients with type 2 diabetes with differences in renal function preservation, comparing patients receiving sodium-glucose co-transporter-2 inhibitors with those receiving dipeptidyl peptidase-4 inhibitors, using a supervised machine-learning algorithm (PROFILE study): A retrospective analysis of a Japanese commercial medical database. Diabetes Obes Metab 2019; 21:1925-1934. [PMID: 31050099 PMCID: PMC6771907 DOI: 10.1111/dom.13753] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2019] [Revised: 04/17/2019] [Accepted: 04/30/2019] [Indexed: 12/25/2022]
Abstract
AIMS To investigate the effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors vs. dipeptidyl peptidase-4 (DPP-4) inhibitors on renal function preservation (RFP) using real-world data of patients with type 2 diabetes in Japan, and to identify which subgroups of patients obtained greater RFP benefits with SGLT2 inhibitors vs. DPP-4 inhibitors. METHODS We retrospectively analysed claims data recorded in the Medical Data Vision database in Japan of patients with type 2 diabetes (aged ≥18 years) prescribed any SGLT2 inhibitor or any DPP-4 inhibitor between May 2014 and September 2016 (identification period), in whom estimated glomerular filtration rate (eGFR) was measured at least twice (baseline, up to 6 months before the index date; follow-up, 9 to 15 months after the index date) with continuous treatment until the follow-up eGFR. The endpoint was the percentage of patients with RFP, defined as no change or an increase in eGFR from baseline to follow-up. A proprietary supervised learning algorithm (Q-Finder; Quinten, Paris, France) was used to identify the profiles of patients with an additional RFP benefit of SGLT2 inhibitors vs. DPP-4 inhibitors. RESULTS Data were available for 990 patients prescribed SGLT2 inhibitors and 4257 prescribed DPP-4 inhibitors. The proportion of patients with RFP was significantly greater in the SGLT2 inhibitor group (odds ratio 1.27; P = 0.01). The Q-Finder algorithm identified four clinically relevant subgroups showing superior RFP with SGLT2 inhibitors (P < 0.1): no hyperlipidaemia and eGFR ≥79 mL/min/1.73 m2 ; eGFR ≥79 mL/min/1.73 m2 and diabetes duration ≤1.2 years; eGFR ≥75 mL/min/1.73 m2 and use of antithrombotic agents; and haemoglobin ≤13.4 g/dL and LDL cholesterol ≥95.1 mg/dL. In each profile, glycaemic control was similar in the two groups. CONCLUSION SGLT2 inhibitors were associated with more favourable RFP vs. DPP-4 inhibitors in patients with certain profiles in real-world settings in Japan.
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Affiliation(s)
- Fang L. Zhou
- Real World Evidence Generation, SanofiBridgewaterNew Jersey
| | - Hirotaka Watada
- Department of Metabolism and Endocrinology, Juntendo University Graduate School of MedicineTokyoJapan
| | | | | | - Dian Kang
- Data Science Consulting, QuintenParisFrance
| | | | | | - Hiroshi Maegawa
- Department of Medicine, Shiga University of Medical ScienceOtsuJapan
| | - Daisuke Koya
- Department of Diabetology and Endocrinology, Kanazawa Medical UniversityUchinadaJapan
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24
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Lamos EM, Hedrington M, Davis SN. An update on the safety and efficacy of oral antidiabetic drugs: DPP-4 inhibitors and SGLT-2 inhibitors. Expert Opin Drug Saf 2019; 18:691-701. [DOI: 10.1080/14740338.2019.1626823] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- Elizabeth Mary Lamos
- Division of Endocrinology, Diabetes and Metabolism, University of Maryland School of Medicine, Baltimore,
MD, USA
| | - Maka Hedrington
- Division of Endocrinology, Diabetes and Metabolism, University of Maryland School of Medicine, Baltimore,
MD, USA
| | - Stephen N Davis
- Department of Medicine, University of Maryland Medical Center, Baltimore,
MD, USA
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25
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Boeder S, Edelman SV. Sodium-glucose co-transporter inhibitors as adjunctive treatment to insulin in type 1 diabetes: A review of randomized controlled trials. Diabetes Obes Metab 2019; 21 Suppl 2:62-77. [PMID: 31081593 PMCID: PMC6899736 DOI: 10.1111/dom.13749] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 04/11/2019] [Accepted: 04/12/2019] [Indexed: 02/06/2023]
Abstract
Many patients with type 1 diabetes (T1D) struggle to achieve glycaemic control and experience significant fluctuations in glucose concentrations, despite insulin treatment. Sodium-glucose co-transporter (SGLT)-2 inhibitors and dual SGLT-1/2 inhibitors increase glucose elimination via the kidneys and reduce hyperglycaemia via insulin-independent mechanisms. This review examines available efficacy and safety data for these agents under investigation as adjunctive therapy for T1D. Across randomized trials of up to 52 weeks, SGLT-2 inhibitors or SGLT-1/2 inhibitors as an adjunct to insulin demonstrated significant reductions in glycated haemoglobin, glucose exposure, and measures of glycaemic variability, as well as increased time in the target glycaemic range, compared with placebo. Non-glycaemic benefits included reductions in body weight and insulin doses, as well as improvements in some cardiovascular risk factors and treatment satisfaction. SGLT-2 inhibitors and SGLT-1/2 inhibitors were associated with similar rates of hypoglycaemia but a higher incidence of genitourinary infections, compared with placebo. Diabetic ketoacidosis occurred more often with SGLT-2 inhibitors and SGLT-1/2 inhibitors vs placebo, although the incidence was generally low. Risk mitigation strategies in light of clinical trial data are also discussed. Positive data from randomized controlled trials of the SGLT-2 inhibitor dapagliflozin have led to the approval of dapagliflozin as an adjunct to insulin in adults with T1D having body mass index ≥27 kg/m2 in whom insulin does not provide adequate glycaemic control in Europe and to approval as an adjunct to insulin for adults with T1D in Japan.
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Affiliation(s)
- Schafer Boeder
- Division of Endocrinology and MetabolismUniversity of California San DiegoSan DiegoCalifornia
| | - Steven V. Edelman
- Division of Endocrinology and MetabolismUniversity of California San DiegoSan DiegoCalifornia
- Taking Control of Your Diabetes, 501(c)3Solana BeachCalifornia
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26
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Parker ED, Wittbrodt ET, McPheeters JT, Frias JP. Comparison of healthcare resource utilization and costs in patients with type 2 diabetes initiating dapagliflozin versus sitagliptin. Diabetes Obes Metab 2019; 21:227-233. [PMID: 30101553 DOI: 10.1111/dom.13502] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Revised: 08/07/2018] [Accepted: 08/09/2018] [Indexed: 01/10/2023]
Abstract
AIMS To compare healthcare costs and utilization in patients with type 2 diabetes (T2D) who initiated dapagliflozin (DAPA) with costs and utilization in those who initiated sitagliptin (SITA) in a real-world setting. MATERIALS AND METHODS This was a retrospective study of health plan enrollees in two US commercial claims databases or Medicare Part D. The study population comprised adult patients with T2D who initiated DAPA or SITA between January 1, 2014 and April 30, 2015. DAPA and SITA initiators were propensity-score-matched, and healthcare utilization and costs during the 1-year follow-up period were compared. Analyses were conducted separately for patients with evidence of oral antidiabetic drug (OAD) monotherapy use at baseline. RESULTS A total of 2722 patients were included in each matched cohort. Follow-up unadjusted all-cause costs ($16 065 and $17 281; P = 0.135) and diabetes-related costs ($9697 and $9354; P = 0.539) were similar in the DAPA and SITA cohorts. Higher office and outpatient visit costs in the SITA group were offset by higher pharmacy costs in the DAPA group. In the subgroup of 1804 patients with OAD monotherapy use at baseline, patients in the SITA group had higher total all-cause costs compared with those in the DAPA group ($14 884 vs. $12 353; P = 0.026). CONCLUSION Patients who initiated DAPA or SITA had similar all-cause and diabetes-related healthcare costs over 1 year of follow-up. In the subgroup of patients treated with OAD monotherapy at baseline (84% metformin monotherapy), those who initiated DAPA as add-on therapy had lower costs than patients who added SITA.
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Affiliation(s)
- Emily D Parker
- Health Economics and Outcomes Research, Optum, Eden Prairie, Minnesota
| | - Eric T Wittbrodt
- Health Economics and Outcomes Research, AstraZeneca, Wilmington, Delaware
| | | | - Juan P Frias
- National Research Institute, Los Angeles, California
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27
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Willis M, Asseburg C, Neslusan C. Conducting and interpreting results of network meta-analyses in type 2 diabetes mellitus: A review of network meta-analyses that include sodium glucose co-transporter 2 inhibitors. Diabetes Res Clin Pract 2019; 148:222-233. [PMID: 30641163 DOI: 10.1016/j.diabres.2019.01.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Revised: 12/04/2018] [Accepted: 01/04/2019] [Indexed: 11/27/2022]
Abstract
AIMS Network meta-analyses (NMAs) are valuable ways to generate comparative effectiveness data for therapies available to treat type 2 diabetes mellitus (T2DM). This review assesses NMAs that evaluate sodium glucose co-transporter 2 (SGLT2) inhibitors for treatment of T2DM and discusses potential issues in conducting and interpreting NMAs. METHODS A systematic literature search was conducted on September 13, 2018 using the search terms "network meta-analysis," "SGLT2," variations of these terms, and individual SGLT2 inhibitor names. Extracted data included NMA objectives, methods, target populations, treatments, study endpoints, length of follow-up, and funding. Differences between NMAs were investigated. RESULTS Thirty-five full-length publications met criteria for inclusion. In most NMAs, the target population was defined by therapeutic regimen (e.g., combination with metformin). Follow-up intervals permitted in NMAs varied considerably (range, 4-208 weeks). Twenty-nine NMAs included dapagliflozin, 28 evaluated canagliflozin, and 27 evaluated empagliflozin. Nine NMAs used frequentist methods; 16 used Bayesian methods. Six NMAs were funded by pharmaceutical manufacturers. Heterogeneity across NMAs was seen in scope, time frame, and other aspects of analytic design. CONCLUSIONS Although this review indicates that methodological guidelines for reporting NMAs were generally followed, it also emphasizes the need for T2DM-specific guidance requiring clear reporting of NMA scope and objectives to aid appropriate interpretation and use of NMA results.
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Affiliation(s)
- Michael Willis
- The Swedish Institute for Health Economics, Box 2127, Lund 220 02, Sweden.
| | - Christian Asseburg
- The Swedish Institute for Health Economics, Box 2127, Lund 220 02, Sweden.
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28
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Ling J, Ge L, Zhang DH, Wang YF, Xie ZL, Tian JH, Xiao XH, Yang KH. DPP-4 inhibitors for the treatment of type 2 diabetes: a methodology overview of systematic reviews. Acta Diabetol 2019; 56:7-27. [PMID: 29858660 DOI: 10.1007/s00592-018-1164-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2018] [Accepted: 05/19/2018] [Indexed: 12/19/2022]
Abstract
AIMS To evaluate the methodological quality of systematic reviews (SRs), and summarize evidence of important outcomes from dipeptidyl peptidase-4 inhibitors (DPP4-I) in treating type 2 diabetes mellitus (T2DM). METHODS We included SRs of DPP4-I for the treatment of T2DM until January, 2018 by searching the Cochrane Library, PubMed, EMBASE and three Chinese databases. We evaluated the methodological qualities with the AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool and the GRADE (The Grading of Recommendations Assessment, Development and Evaluation) approach. RESULTS Sixty-three SRs (a total of 2,603,140 participants) receiving DPP4-I for the treatment of T2DM were included. The results of AMSTAR showed that the lowest quality was "a list of studies (included and excluded) item" with only one (1.6%) study provided, followed by the "providing a priori design" item with only four (6.3%) studies conforming to this item, the next were "the status of publication (gray literature) used as an inclusion criterion item", with only 18 (28.9%) studies conforming to these items. Only seven (11.1%) studies scored more than nine points in AMSTAR, indicating high methodological quality. For GRADE, of the 128 outcomes, high quality evidence was provided in only 28 (21.9%), moderate in 70 (54.7%), low in 27 (21.1%), and very low in three (2.3%). CONCLUSIONS The methodological quality of SRs of DPP4-I for type 2 diabetes mellitus is not high and there are common areas for improvement. Furthermore, the quality of evidence level is moderate and more high quality evidence is needed.
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Affiliation(s)
- Juan Ling
- School of Basic Medical Sciences, Evidence-Based Medicine Center, Lanzhou University, Lanzhou, China
- Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou, China
- Chinese GRADE Center, Lanzhou University, Lanzhou, China
- WHO Collaborating Center for Guideline Implementation and Knowledge Translation, Lanzhou, China
| | - Long Ge
- School of Basic Medical Sciences, Evidence-Based Medicine Center, Lanzhou University, Lanzhou, China
- Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou, China
- Chinese GRADE Center, Lanzhou University, Lanzhou, China
- WHO Collaborating Center for Guideline Implementation and Knowledge Translation, Lanzhou, China
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
| | - Ding-Hua Zhang
- Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Yong-Feng Wang
- School of Basic Medical Sciences, Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Zhuo-Lin Xie
- Department of Endocrinology, Gansu Province Hospital of Traditional Chinese Medicine, Lanzhou, China
| | - Jin-Hui Tian
- School of Basic Medical Sciences, Evidence-Based Medicine Center, Lanzhou University, Lanzhou, China
- Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou, China
- Chinese GRADE Center, Lanzhou University, Lanzhou, China
- WHO Collaborating Center for Guideline Implementation and Knowledge Translation, Lanzhou, China
| | | | - Ke-Hu Yang
- School of Basic Medical Sciences, Evidence-Based Medicine Center, Lanzhou University, Lanzhou, China.
- Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou, China.
- Chinese GRADE Center, Lanzhou University, Lanzhou, China.
- WHO Collaborating Center for Guideline Implementation and Knowledge Translation, Lanzhou, China.
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29
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Wang N, Yang T, Li J, Zhang X. Dipeptidyl peptidase-4 inhibitors as add-on therapy to insulin in patients with type 2 diabetes mellitus: a meta-analysis of randomized controlled trials. Diabetes Metab Syndr Obes 2019; 12:1513-1526. [PMID: 31692532 PMCID: PMC6710543 DOI: 10.2147/dmso.s202024] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Accepted: 06/07/2019] [Indexed: 12/15/2022] Open
Abstract
PURPOSE Addition of the dipeptidyl peptidase-4 (DPP4) inhibitors to insulin in patients with type 2 diabetes mellitus (T2DM) may achieve better glycemic control. However, results of pilot randomized controlled trials (RCTs) are inconsistent. We aimed to perform a meta-analysis of RCTs to evaluate efficacy and safety of DPP4 inhibitors compared with placebo/no treatment as add-on therapy to insulin in T2DM patients. MATERIALS AND METHODS Relevant studies were identified via a search of PubMed, Cochrane Library, and Embase databases. A fixed or random effect model was applied according to the heterogeneity. RESULTS Overall, 22 RCTs with 6,957 T2DM patients were included. Addition of DPP4 inhibitors to insulin was associated with significantly reduced HbA1c as compared with controls (weighed mean difference [WMD]: -0.54%, p<0.001). The benefits of DPP4 inhibitors as add-on therapy on HbA1c were independent of study design, follow-up duration, categories of DPP4 inhibitors used, and using of fixed/adjustable insulin doses as indicated by predefined subgroup analyses. Moreover, addition of DPP4 inhibitors to insulin was associated with significantly reduced fasting blood glucose (WMD: -0.47mmol/L, p<0.001), postprandial glucose at 2 hrs (WMD: -2.03 mmol/L, p<0.001), and daily dose of insulin (WMD: -2.73U/d, p<0.001), while body weight (WMD: 0.02 g, p=0.81) or risk of symptomatic hypoglycemia (risk ratio: 0.92, p=0.37) were not affected. CONCLUSIONS Addition of DPP4 inhibitors to insulin significantly improved the glycemic control in T2DM patients without further increasing the risk of weight gain and hypoglycemia.
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Affiliation(s)
- Na Wang
- Department of Endocrinology, The Affiliated Hospital of Jining Medical University, Jining272000, People’s Republic of China
- Correspondence: Na WangDepartment of Endocrinology, The Affiliated Hospital of Jining Medical University, No. 89 Guhuai Road, Jining272000, People’s Republic of ChinaTel +86 0 537 290 3399Fax +86 0 537 290 3399Email
| | - Tao Yang
- The 4th Department of Psychiatry, Jining Psychiatric Hospital, Jining272000, People’s Republic of China
| | - Jie Li
- The 4th Department of Psychiatry, Jining Psychiatric Hospital, Jining272000, People’s Republic of China
| | - Xianfeng Zhang
- The 4th Department of Psychiatry, Jining Psychiatric Hospital, Jining272000, People’s Republic of China
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30
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Davies MJ, D'Alessio DA, Fradkin J, Kernan WN, Mathieu C, Mingrone G, Rossing P, Tsapas A, Wexler DJ, Buse JB. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2018; 61:2461-2498. [PMID: 30288571 DOI: 10.1007/s00125-018-4729-5] [Citation(s) in RCA: 786] [Impact Index Per Article: 112.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the prior position statements, published in 2012 and 2015, on the management of type 2 diabetes in adults. A systematic evaluation of the literature since 2014 informed new recommendations. These include additional focus on lifestyle management and diabetes self-management education and support. For those with obesity, efforts targeting weight loss, including lifestyle, medication and surgical interventions, are recommended. With regards to medication management, for patients with clinical cardiovascular disease, a sodium-glucose cotransporter-2 (SGLT2) inhibitor or a glucagon-like peptide-1 (GLP-1) receptor agonist with proven cardiovascular benefit is recommended. For patients with chronic kidney disease or clinical heart failure and atherosclerotic cardiovascular disease, an SGLT2 inhibitor with proven benefit is recommended. GLP-1 receptor agonists are generally recommended as the first injectable medication.
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Affiliation(s)
- Melanie J Davies
- Diabetes Research Centre, University of Leicester, Leicester, UK.
- Leicester Diabetes Centre, Leicester General Hospital, Leicester,, LE5 4PW, UK.
| | - David A D'Alessio
- Department of Medicine, Duke University School of Medicine, Durham, NC, USA
| | - Judith Fradkin
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Walter N Kernan
- Department of Medicine, Yale School of Medicine, New Haven, CT, USA
| | - Chantal Mathieu
- Clinical and Experimental Endocrinology, UZ Gasthuisberg, KU Leuven, Leuven, Belgium
| | - Geltrude Mingrone
- Department of Internal Medicine, Catholic University, Rome, Italy
- Diabetes and Nutritional Sciences, King's College London, London, UK
| | - Peter Rossing
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
- University of Copenhagen, Copenhagen, Denmark
| | - Apostolos Tsapas
- Second Medical Department, Aristotle University Thessaloniki, Thessaloniki, Greece
| | - Deborah J Wexler
- Department of Medicine and Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - John B Buse
- Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA
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31
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Davies MJ, D'Alessio DA, Fradkin J, Kernan WN, Mathieu C, Mingrone G, Rossing P, Tsapas A, Wexler DJ, Buse JB. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018; 41:2669-2701. [PMID: 30291106 PMCID: PMC6245208 DOI: 10.2337/dci18-0033] [Citation(s) in RCA: 1778] [Impact Index Per Article: 254.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the prior position statements, published in 2012 and 2015, on the management of type 2 diabetes in adults. A systematic evaluation of the literature since 2014 informed new recommendations. These include additional focus on lifestyle management and diabetes self-management education and support. For those with obesity, efforts targeting weight loss, including lifestyle, medication, and surgical interventions, are recommended. With regards to medication management, for patients with clinical cardiovascular disease, a sodium-glucose cotransporter 2 (SGLT2) inhibitor or a glucagon-like peptide 1 (GLP-1) receptor agonist with proven cardiovascular benefit is recommended. For patients with chronic kidney disease or clinical heart failure and atherosclerotic cardiovascular disease, an SGLT2 inhibitor with proven benefit is recommended. GLP-1 receptor agonists are generally recommended as the first injectable medication.
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Affiliation(s)
- Melanie J Davies
- Diabetes Research Centre, University of Leicester, Leicester, U.K.,Leicester Diabetes Centre, Leicester General Hospital, Leicester, U.K
| | - David A D'Alessio
- Department of Medicine, Duke University School of Medicine, Durham, NC
| | - Judith Fradkin
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
| | - Walter N Kernan
- Department of Medicine, Yale School of Medicine, New Haven, CT
| | - Chantal Mathieu
- Clinical and Experimental Endocrinology, UZ Gasthuisberg, KU Leuven, Leuven, Belgium
| | - Geltrude Mingrone
- Department of Internal Medicine, Catholic University, Rome, Italy.,Diabetes and Nutritional Sciences, King's College London, London, U.K
| | - Peter Rossing
- Steno Diabetes Center Copenhagen, Gentofte, Denmark.,University of Copenhagen, Copenhagen, Denmark
| | - Apostolos Tsapas
- Second Medical Department, Aristotle University Thessaloniki, Thessaloniki, Greece
| | - Deborah J Wexler
- Department of Medicine and Diabetes Unit, Massachusetts General Hospital, Boston, MA.,Harvard Medical School, Boston, MA
| | - John B Buse
- Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
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32
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Kalra S, Kesavadev J, Chadha M, Kumar GV. Sodium-glucose Cotransporter-2 Inhibitors in Combination with Other Glucose-lowering Agents for the Treatment of Type 2 Diabetes Mellitus. Indian J Endocrinol Metab 2018; 22:827-836. [PMID: 30766826 PMCID: PMC6330851 DOI: 10.4103/ijem.ijem_162_17] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Involvement of multiple physiological pathways and complex pathogenesis is responsible for the onset and progression of type 2 diabetes mellitus (T2DM). Since it is difficult to manage multiple pathophysiological defects by monotherapy, a combination therapy with two or more oral antidiabetic agents (OADs) may help achieve euglycemia in T2DM patients. Choice of OADs is difficult with growing armamentarium of antidiabetic therapy. Ideally, drug combination should aim at reversal of known pathogenic abnormalities and demonstrate improvement in the overall metabolic health rather than simply reduce glycosylated hemoglobin (HbA1c) levels. Increased glucose reabsorption, a faulty pathological mechanism, is targeted by a novel class of drugs, namely, the sodium-glucose cotransporter-2 (SGLT2) inhibitors. Combination of SGLT2 inhibitors and other OADs complement each other due to their unique mechanism of action. In addition, the glucose-lowering effect of SGLT2 inhibitors remains independent of β-cell function and insulin sensitivity which reduces the chances of severe hypoglycemia in patients receiving these agents. Clinical studies from the past favor the use of SGLT2 inhibitors in combination with other agents to achieve better HbA1c levels, weight loss, and blood pressure control. In this review, we have made an attempt to explore the recommended guidelines for combination therapy, its advantages as either combination therapy or fixed-dose combinations therapy, and the role of SGLT2 inhibitors as a choice of drug as a combination with other OADs.
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Affiliation(s)
- Sanjay Kalra
- Department of Endocrinology, Bharti Hospital and BRIDE, Karnal, Haryana, India
| | - Jothydev Kesavadev
- Department of Diabetes, Jothydev's Diabetes and Research Centre, Thiruvananthapuram, Kerala, India
| | - Manoj Chadha
- P. Hinduja Hospital and Medical Research Centre, Mumbai, Maharashtra, India
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33
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Goldenberg RM, Assimakopoulos P, Gilbert JD, Gottesman IS, Yale JF. A practical approach and algorithm for intensifying beyond basal insulin in type 2 diabetes. Diabetes Obes Metab 2018; 20:2064-2074. [PMID: 29707875 DOI: 10.1111/dom.13337] [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] [Scholar Register] [Received: 03/10/2018] [Revised: 04/09/2018] [Accepted: 04/24/2018] [Indexed: 11/29/2022]
Abstract
Despite the availability of long-term data demonstrating the benefits of timely and aggressive intensification of antihyperglycaemic regimens among individuals with type 2 diabetes, intensification beyond basal insulin continues to be suboptimal and a global challenge. This review summarizes the evidence surrounding the various options of advancing glucose-lowering management beyond basal insulin and provides a practical algorithm to assist in optimizing patient care and enhancing glycaemic target achievements.
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Affiliation(s)
| | - Peter Assimakopoulos
- Division of Endocrinology and Metabolism, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
| | - Jeremy D Gilbert
- Division of Endocrinology and Metabolism, Sunnybrook Health Sciences Centre, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Irving S Gottesman
- Trillium Health Partners, Credit Valley Hospital, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Jean-François Yale
- Division of Endocrinology and Metabolism, McGill University Health Centre, McGill University and LMC Diabetes and Endocrinology, Montreal, Quebec, Canada
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34
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Billings LK, Parkin CG, Price D. Baseline Glycated Hemoglobin Values Predict the Magnitude of Glycemic Improvement in Patients with Type 1 and Type 2 Diabetes: Subgroup Analyses from the DIAMOND Study Program. Diabetes Technol Ther 2018; 20:561-565. [PMID: 30044123 PMCID: PMC6080123 DOI: 10.1089/dia.2018.0163] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
The DIAMOND study demonstrated that the addition of real-time continuous glucose monitoring (rtCGM) effectively lowers glycated hemoglobin (HbA1c) in patients with type 1 (T1D) and type 2 diabetes (T2D), treated with multiple daily injections (MDI). This post hoc analysis investigated whether DIAMOND study participants at progressively higher baseline HbA1c levels benefit from using rtCGM. We examined outcomes data from a large, randomized, controlled trial of MDI-treated participants with T1D (N = 158) and T2D (N = 158), comparing monitoring by rtCGM versus self-monitoring of blood glucose (SMBG). The primary outcome was the magnitude of HbA1c reductions among study participants within elevated baseline HbA1c levels (≥8.0%-10.0%, ≥8.5%-10.0%, and ≥9.0%-10.0%). Analyses were performed on three subgroups: T1D, T2D, and combined T1D/T2D. The full T1D analysis population had a mean baseline HbA1c value of 8.6 ± 0.6% (range 7.5%-9.9%), randomized to rtCGM (n = 105) or control (n = 53). The full T2D analysis population had a mean baseline HbA1c value of 8.5 ± 0.6% (range 7.5%-9.9%), randomized to rtCGM (n = 79) or control (n = 79). Participants had improvements in glycemic status regardless of monitoring method. In the three subgroups, the change in HbA1c was significantly greater in rtCGM participants compared to SMBG at all predefined baseline HbA1c levels at 12 and 24 weeks. Among the rtCGM participants, the change in HbA1c was numerically greatest at the highest baseline HbA1c subgroup (≥9.0%). Participants with elevated baseline HbA1c had improvements in glycemic status regardless of monitoring method. However, the magnitudes of improvements appeared greater among participants using rtCGM.
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Affiliation(s)
- Liana K. Billings
- Department of Clinical, NorthShore University HealthSystem, Skokie, Illinois
- University of Chicago Pritzker School of Medicine, Chicago, Illinois
| | - Christopher G. Parkin
- Department of Research, CGParkin Communications, Inc., Boulder City, Nevada
- Address correspondence to:Christopher G. Parkin, MSDepartment of ResearchCGParkin Communications, Inc.932 Vista Lago WayBoulder City, NV 89005
| | - David Price
- Department of Medical Affairs, Dexcom, Inc., San Diego, California
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35
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Yang W, Cai X, Gao X, Chen Y, Chen L, Ji L. Addition of dipeptidyl peptidase-4 inhibitors to insulin treatment in type 2 diabetes patients: A meta-analysis. J Diabetes Investig 2018; 9:813-821. [PMID: 29047219 PMCID: PMC6031492 DOI: 10.1111/jdi.12764] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 09/25/2017] [Accepted: 10/09/2017] [Indexed: 12/30/2022] Open
Abstract
AIMS/INTRODUCTION To evaluate the efficacy and safety of combining insulin therapy with dipeptidyl peptidase-4 (DPP-4) inhibitors compared with combining insulin therapy with a placebo or other antihyperglycemic agents. MATERIALS AND METHODS A literature search was carried out via electronic databases. The inclusion criteria were randomized controlled trials comparing the addition of DPP-4 inhibitors to insulin with the addition of a placebo or other active hypoglycemic agents to insulin therapy, study duration of no less than 12 weeks carried out in type 2 diabetes patients and the availability of outcome data to evaluate a change in the glycated hemoglobin. RESULTS The glycated hemoglobin-lowering efficacy was significantly greater with DPP-4 inhibitor/insulin (DPP-4i/INS) than with placebo/insulin (weighted mean difference -0.53%, 95% confidence interval -0.63, -0.43, P < 0.01). The postprandial plasma glucose-lowering efficacies was also significantly greater with DPP-4i/INS than with placebo/insulin (weighted mean difference -1.65 mmol/L, 95% CI: -2.34, -0.96, P < 0.05). The risk of hypoglycemia or severe hypoglycemia was similar for DPP4i/INS and placebo/insulin treatments. There was no significant difference in the glycemia-lowering efficacy between DPP-4i/INS and alpha-glucosidase inhibitors/insulin, thiazolidinedione/insulin and glucagon-like peptide-1 receptor agonist/insulin. Sodium-glucose cotransporter 2 inhibitor/insulin treatment achieved better placebo-corrected efficacy in lowering postprandial plasma glucose, with less weight gain and no higher risk of hypoglycemia. CONCLUSIONS Treatment with DPP-4 inhibitors combined with insulin improved glycemic control without an increased risk of hypoglycemia or weight gain compared with insulin treatment alone.
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Affiliation(s)
- Wenjia Yang
- Endocrinology and Metabolism DepartmentPeking University People's HospitalBeijingChina
| | - Xiaoling Cai
- Endocrinology and Metabolism DepartmentPeking University People's HospitalBeijingChina
| | - Xueying Gao
- Endocrinology and Metabolism DepartmentPeking University People's HospitalBeijingChina
| | - Yifei Chen
- Endocrinology and Metabolism DepartmentPeking University People's HospitalBeijingChina
| | - Ling Chen
- Endocrinology and Metabolism DepartmentPeking University People's HospitalBeijingChina
| | - Linong Ji
- Endocrinology and Metabolism DepartmentPeking University People's HospitalBeijingChina
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Avogaro A, Delgado E, Lingvay I. When metformin is not enough: Pros and cons of SGLT2 and DPP-4 inhibitors as a second line therapy. Diabetes Metab Res Rev 2018; 34:e2981. [PMID: 29320602 DOI: 10.1002/dmrr.2981] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Revised: 11/28/2017] [Accepted: 12/21/2017] [Indexed: 12/23/2022]
Abstract
The newer oral therapies for type 2 diabetes mellitus, dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium glucose cotransporter 2 (SGLT2) inhibitors, have advantages over older agents. Dipeptidyl peptidase-4 inhibitors are weight neutral and have few adverse effects. Sodium glucose cotransporter 2 inhibitors have additional benefits: weight loss, blood pressure reduction, cardiovascular risk reduction, and renoprotective effects. Sodium glucose cotransporter 2 inhibitors have increased risk of urogenital infections and possible risk of "euglycaemic" diabetic ketoacidosis. It is important to balance the benefits over the older-oral therapies as these agents are more expensive; yet some analyses suggest that they are within the limits of what is considered cost-effective in health care. We discuss the relative merits and drawbacks of these 2 classes and consider their roles in the treatment of type 2 diabetes mellitus. We suggest a number of patient profiles where early use of these agents could be used. We favour the use of SGLT2 inhibitors over DPP-4 inhibitors as add on therapy to metformin when glycaemic targets have not been achieved given their similar glycaemic efficacy and the additional benefits of SGLT2 inhibitors. We particularly favour SGLT2 inhibitors in those where additional weight loss and blood pressure reductions are desired, and in patients with heart failure or cardiovascular disease. Care should be taken to warn patients about genital fungal infections and to avoid use in people with risk factors for SGLT2 associated ketoacidosis. We favour DPP-4 inhibitors in those where side effects of other agents are of concern, the frail elderly population, and those with renal disease precluding SGTL2 inhibitor use.
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Affiliation(s)
- Angelo Avogaro
- Department of Internal Medicine, Unit of Metabolic Disease, University of Padova, Padova, Italy
| | - Elías Delgado
- Department of Endocrinology and Nutrition, University of Oviedo, Oviedo, Spain
- Endocrinology and Nutrition Department, Hospital Universitario Central de Asturias, Oviedo, Spain
- Metabolism Unit, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Asturias, Spain
| | - Ildiko Lingvay
- Internal Medicine/Endocrinology and Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA
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d'Emden M, Amerena J, Deed G, Pollock C, Cooper ME. SGLT2 inhibitors with cardiovascular benefits: Transforming clinical care in Type 2 diabetes mellitus. Diabetes Res Clin Pract 2018; 136:23-31. [PMID: 29196150 DOI: 10.1016/j.diabres.2017.11.023] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Revised: 11/07/2017] [Accepted: 11/20/2017] [Indexed: 01/05/2023]
Abstract
Cardiovascular risk reduction in individuals with Type 2 diabetes mellitus (T2DM) is a key part of clinical management. Sodium-glucose co-transporter (SGLT2) inhibitors improve glycaemic control, reduce body weight and decrease blood pressure. In addition, the SGLT2 inhibitors empagliflozin and canagliflozin reduced the risk of composite cardiovascular events in high-risk individuals with T2DM in the EMPA-REG OUTCOME trial and the CANVAS Program, respectively. Empagliflozin also reduced cardiovascular deaths and improved renal outcomes. This class of agents should be considered in people with established cardiovascular disease, usually in combination with other glucose lowering medications, when satisfactory glycaemic control has not been achieved. The dose of insulin or sulfonylureas may need to be lowered when used with SGLT2 inhibitors, to reduce the risk of hypoglycaemia. Genitourinary infections can occur with SGLT2 inhibitors in a small proportion of people. In people with osteoporosis or prior amputation, it may be prudent to use empagliflozin rather than canagliflozin, based on the increased risk for bone fractures and amputations observed with canagliflozin in the CANVAS Program. SGLT2 inhibitors have the potential to transform the clinical care of persons with T2DM by not only improving glycaemic control but also reducing blood pressure, body weight and diabetes-related end-organ complications.
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Affiliation(s)
- Michael d'Emden
- Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
| | | | - Gary Deed
- Mediwell Medical Clinic, Coorparoo, QLD, Australia
| | - Carol Pollock
- Kolling Institute, Royal North Shore Hospital, University of Sydney, Sydney, NSW, Australia
| | - Mark E Cooper
- Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC, Australia.
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38
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Woo VC, Berard LD, Bajaj HS, Ekoé JM, Senior PA. Considerations for Initiating a Sodium-Glucose Co-Transporter 2 Inhibitor in Adults With Type 2 Diabetes Using Insulin. Can J Diabetes 2018; 42:88-93. [DOI: 10.1016/j.jcjd.2017.01.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2017] [Revised: 01/25/2017] [Accepted: 01/27/2017] [Indexed: 01/11/2023]
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39
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Lee BW, Kim JH, Ko SH, Hur KY, Kim NH, Rhee SY, Kim HJ, Moon MK, Park SO, Choi KM. Insulin therapy for adult patients with type 2 diabetes mellitus: a position statement of the Korean Diabetes Association, 2017. Korean J Intern Med 2017; 32:967-973. [PMID: 29057642 PMCID: PMC5668405 DOI: 10.3904/kjim.2017.314] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2017] [Accepted: 10/14/2017] [Indexed: 11/27/2022] Open
Abstract
The Korean Diabetes Association (KDA) has regularly updated its Clinical Practice Guidelines. In 2017, the KDA published a position statement on the use of antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM). Growing evidence from new multinational clinical trials using novel and traditional insulin analogues has also been accumulated. Following global trends, many results of clinical trials, especially concerning the clinical efficacy and safety of insulin therapy, have been published about Korean patients with T2DM. After a systematic search of recent evidence, the KDA updated and modified its clinical practice recommendations regarding the initiation, choice, and intensification of insulin and created an insulin treatment algorithm for the first time to guide physicians caring for adult Korean patients with T2DM.
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Affiliation(s)
- Byung-Wan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jin Hwa Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chosun University College of Medicine, Gwangju, Korea
| | - Seung-Hyun Ko
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Correspondence to Seung-Hyun Ko, M.D. Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, St. Vincent's Hospital, The Catholic University of Korea, 93 Jungbu-daero, Paldal-gu, Suwon 16247, Korea Tel: +82-31-249-8155 Fax: +82-31-253-8898 E-mail:
| | - Kyu Yeon Hur
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Nan-Hee Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Sang Youl Rhee
- Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Korea
| | - Hyun Jin Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea
| | - Min Kyong Moon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Seok-O Park
- Department of Internal Medicine, Gwangmyeong Sungae Hospital, Gwangmyeong, Korea
| | - Kyung Mook Choi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
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40
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Ko SH, Hur KY, Rhee SY, Kim NH, Moon MK, Park SO, Lee BW, Kim HJ, Choi KM, Kim JH. Antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus 2017: a position statement of the Korean Diabetes Association. Korean J Intern Med 2017; 32:947-958. [PMID: 29056038 PMCID: PMC5668403 DOI: 10.3904/kjim.2017.298] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2017] [Accepted: 09/15/2017] [Indexed: 12/12/2022] Open
Abstract
In 2017, the Korean Diabetes Association (KDA) published a position statement on the use of antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM). The KDA regularly updates its Clinical Practice Guidelines, but since the last update in 2015, many results from clinical trials have been introduced, and domestic data from studies performed in Korean patients with T2DM have been published. Recently, evidence from large clinical studies assessing cardiovascular outcomes following the use of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM were incorporated into the recommendations. Additionally, new data from clinical trials using dipeptidyl peptidase 4 inhibitors and thiazolidinediones in Korean patients with T2DM were added. Following a systematic review and assessment of recent evidence, the KDA updated and modified its clinical practice recommendations regarding the use of antihyperglycemic agents and revised the treatment algorithm for Korean adult patients with T2DM.
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Affiliation(s)
- Seung-Hyun Ko
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kyu Yeon Hur
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sang Youl Rhee
- Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Korea
| | - Nan-Hee Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Min Kyong Moon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Seok-O Park
- Department of Internal Medicine, Gwangmyeong Sungae Hospital, Gwangmyeong, Korea
| | - Byung-Wan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Hyun Jin Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea
| | - Kyung Mook Choi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Jin Hwa Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chosun University College of Medicine, Gwangju, Korea
| | - Committee of Clinical Practice Guideline of Korean Diabetes Association
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
- Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
- Department of Internal Medicine, Gwangmyeong Sungae Hospital, Gwangmyeong, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chosun University College of Medicine, Gwangju, Korea
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41
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Ko SH, Hur KY, Rhee SY, Kim NH, Moon MK, Park SO, Lee BW, Kim HJ, Choi KM, Kim JH. Antihyperglycemic Agent Therapy for Adult Patients with Type 2 Diabetes Mellitus 2017: A Position Statement of the Korean Diabetes Association. Diabetes Metab J 2017; 41:337-348. [PMID: 29086531 PMCID: PMC5663672 DOI: 10.4093/dmj.2017.41.5.337] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2017] [Accepted: 09/15/2017] [Indexed: 12/15/2022] Open
Abstract
In 2017, the Korean Diabetes Association (KDA) published a position statement on the use of antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM). The KDA regularly updates its Clinical Practice Guidelines, but since the last update in 2015, many results from clinical trials have been introduced, and domestic data from studies performed in Korean patients with T2DM have been published. Recently, evidence from large clinical studies assessing cardiovascular outcomes following the use of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM were incorporated into the recommendations. Additionally, new data from clinical trials using dipeptidyl peptidase 4 inhibitors and thiazolidinediones in Korean patients with T2DM were added. Following a systematic review and assessment of recent evidence, the KDA updated and modified its clinical practice recommendations regarding the use of antihyperglycemic agents and revised the treatment algorithm for Korean adult patients with T2DM.
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Affiliation(s)
- Seung Hyun Ko
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kyu Yeon Hur
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sang Youl Rhee
- Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Korea
| | - Nan Hee Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Min Kyong Moon
- Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Seok O Park
- Department of Internal Medicine, Gwangmyeong Sungae Hospital, Gwangmyeong, Korea
| | - Byung Wan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Hyun Jin Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea
| | - Kyung Mook Choi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
| | - Jin Hwa Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chosun University College of Medicine, Gwangju, Korea
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42
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Lee BW, Kim JH, Ko SH, Hur KY, Kim NH, Rhee SY, Kim HJ, Moon MK, Park SO, Choi KM. Insulin Therapy for Adult Patients with Type 2 Diabetes Mellitus: A Position Statement of the Korean Diabetes Association, 2017. Diabetes Metab J 2017; 41:367-373. [PMID: 29086534 PMCID: PMC5663675 DOI: 10.4093/dmj.2017.41.5.367] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2017] [Accepted: 09/25/2017] [Indexed: 12/16/2022] Open
Abstract
The Korean Diabetes Association (KDA) has regularly updated its Clinical Practice Guidelines. In 2017, the KDA published a position statement on the use of antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM). Growing evidence from new multinational clinical trials using novel and traditional insulin analogues has also been accumulated. Following global trends, many results of clinical trials, especially concerning the clinical efficacy and safety of insulin therapy, have been published about Korean patients with T2DM. After a systematic search of recent evidence, the KDA updated and modified its clinical practice recommendations regarding the initiation, choice, and intensification of insulin and created an insulin treatment algorithm for the first time to guide physicians caring for adult Korean patients with T2DM.
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Affiliation(s)
- Byung Wan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jin Hwa Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chosun University College of Medicine, Gwangju, Korea
| | - Seung Hyun Ko
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
| | - Kyu Yeon Hur
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Nan Hee Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Sang Youl Rhee
- Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Korea
| | - Hyun Jin Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea
| | - Min Kyong Moon
- Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Seok O Park
- Department of Internal Medicine, Gwangmyeong Sungae Hospital, Gwangmyeong, Korea
| | - Kyung Mook Choi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
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43
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Sa-Nguanmoo P, Tanajak P, Kerdphoo S, Jaiwongkam T, Pratchayasakul W, Chattipakorn N, Chattipakorn SC. SGLT2-inhibitor and DPP-4 inhibitor improve brain function via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in HFD-induced obese rats. Toxicol Appl Pharmacol 2017; 333:43-50. [PMID: 28807765 DOI: 10.1016/j.taap.2017.08.005] [Citation(s) in RCA: 186] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2017] [Revised: 08/02/2017] [Accepted: 08/10/2017] [Indexed: 02/07/2023]
Abstract
Dipeptidyl peptidase-4 inhibitor (vildagliptin) has been shown to exert beneficial effects on insulin sensitivity and neuroprotection in obese-insulin resistance. Recent studies demonstrated the neuroprotection of the sodium-glucose co-transporter 2 inhibitor (dapagliflozin) in diabetes. However, the comparative effects of both drugs and a combination of two drugs on metabolic dysfunction and brain dysfunction impaired by the obese-insulin resistance have never been investigated. Forty male Wistar rats were divided into two groups, and received either a normal-diet (ND, n=8) or a high-fat diet (HFD, n=32) for 16weeks. At week 13, the HFD-fed rats were divided into four subgroups (n=8/subgroup) to receive either a vehicle, vildagliptin (3mg/kg/day) dapagliflozin (1mg/kg/day) or combined drugs for four weeks. ND rats were given a vehicle for four weeks. Metabolic parameters and brain function were investigated. The results demonstrated that HFD rats developed obese-insulin resistance and cognitive decline. Dapagliflozin had greater efficacy on improved peripheral insulin sensitivity and reduced weight gain than vildagliptin. Single therapy resulted in equally improved brain mitochondrial function, insulin signaling, apoptosis and prevented cognitive decline. However, only dapagliflozin improved hippocampal synaptic plasticity. A combination of the drugs had greater efficacy in improving brain insulin sensitivity and reducing brain oxidative stress than the single drug therapy. These findings suggested that dapagliflozin and vildagliptin equally prevented cognitive decline in the obese-insulin resistance, possibly through some similar mechanisms. Dapagliflozin had greater efficacy than vildagliptin for preserving synaptic plasticity, thus combined drugs could be the best therapeutic approach for neuroprotection in the obese-insulin resistance.
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Affiliation(s)
- Piangkwan Sa-Nguanmoo
- Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Pongpan Tanajak
- Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Sasiwan Kerdphoo
- Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Thidarat Jaiwongkam
- Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Wasana Pratchayasakul
- Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Nipon Chattipakorn
- Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand
| | - Siriporn C Chattipakorn
- Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand; Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
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Kadowaki T, Kondo K, Sasaki N, Miyayama K, Yokota S, Terata R, Gouda M. Efficacy and safety of teneligliptin add-on to insulin monotherapy in Japanese patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled trial with an open-label period. Expert Opin Pharmacother 2017; 18:1291-1300. [DOI: 10.1080/14656566.2017.1359259] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Takashi Kadowaki
- Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo , Tokyo, Japan
| | - Kazuoki Kondo
- Integrated Value Development, Mitsubishi Tanabe Pharma Corporation , Tokyo, Japan
| | - Noriyuki Sasaki
- Integrated Value Development, Mitsubishi Tanabe Pharma Corporation , Tokyo, Japan
| | - Kyoko Miyayama
- Integrated Value Development, Mitsubishi Tanabe Pharma Corporation , Tokyo, Japan
| | - Shoko Yokota
- Integrated Value Development, Mitsubishi Tanabe Pharma Corporation , Tokyo, Japan
| | - Ryuji Terata
- Integrated Value Development, Mitsubishi Tanabe Pharma Corporation , Tokyo, Japan
| | - Maki Gouda
- Integrated Value Development, Mitsubishi Tanabe Pharma Corporation , Tokyo, Japan
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