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Peng XV, Klingensmith G, Hsia DS, Xie Y, Czerniak R, Tamborlane WV, Shah AS. A Randomized Phase 3 Study Evaluating the Efficacy and Safety of Alogliptin in Pediatric Participants with Type 2 Diabetes Mellitus. Diabetes Ther 2025; 16:865-883. [PMID: 40032809 DOI: 10.1007/s13300-025-01700-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 01/22/2025] [Indexed: 03/05/2025] Open
Abstract
INTRODUCTION There is an unmet need for pharmacological therapies for children with type 2 diabetes mellitus (T2DM). We assessed the efficacy and safety of an oral dipeptidyl peptidase-4 inhibitor, alogliptin, 25 mg once daily (QD), as a potential treatment for pediatric patients with T2DM. METHODS This phase 3, 52-week, multicenter, randomized, double-blind, placebo-controlled trial was conducted in children and adolescents (10-17 years old) with T2DM. Participants had glycosylated hemoglobin (HbA1c) ≥ 6.5% at baseline (≥ 6.5% to < 11% without treatment or on metformin alone; ≥ 7.0% to < 11% on insulin alone or in combination with metformin). Where required, participants underwent prerandomization stabilization of their background metformin and/or insulin therapy. All received diabetes education and home glucose-monitoring training (during screening, prerandomization stabilization, and specified visits through week 26). Participants were then stratified based on previous antihyperglycemic therapy for 12 weeks before screening into schedule A (antihyperglycemic treatment-naïve) or B (metformin and/or insulin). The primary efficacy endpoint was change in HbA1c levels from baseline at week 26. Safety was assessed as a secondary endpoint at week 52. RESULTS Overall, 152 participants (median age, 14 years; 68.9% female) were randomized (1:1) to receive either alogliptin (n = 75) or placebo (n = 77). The majority were white (58.3%), had a body mass index of ≥ 30 kg/m2 (60.3%), and had received previous antihyperglycemic therapy (82.1%). The difference in HbA1c levels from baseline to week 26 between the alogliptin and placebo groups (least squares mean change [95% confidence interval]) was 0.10 (- 0.63, 0.83; p = 0.78). There was no difference in efficacy endpoints between alogliptin and placebo across both subgroups. No new safety concerns were observed with alogliptin treatment. CONCLUSION Alogliptin 25 mg QD did not significantly improve glycemic control versus placebo in pediatric patients with T2DM. Alogliptin treatment was safe and well tolerated, and no new safety concerns were observed in this study. TRIAL REGISTRATION ClinicalTrials.gov: NCT02856113; EudraCT: 2015-000208-25.
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Affiliation(s)
- Xuejun Victor Peng
- Marketed Products Development, Global Portfolio Division, Takeda Pharmaceuticals Company Limited, Cambridge, MA, USA
| | | | - Daniel S Hsia
- Pennington Biomedical Research Center, Baton Rouge, LA, USA
| | - Yunlong Xie
- Statistics and Quantitative Science, Takeda Pharmaceuticals Company Limited, Cambridge, MA, USA
| | - Richard Czerniak
- Quantitative Clinical Pharmacology, Takeda Pharmaceuticals Company Limited, Cambridge, MA, USA
| | - William V Tamborlane
- Department of Pediatrics and General Clinical Research Center, Yale University School of Medicine, New Haven, CT, USA
| | - Amy S Shah
- Division of Pediatric Endocrinology, Cincinnati Children's Hospital Medical Center, The University of Cincinnati, 3333 Burnet Ave, ML 7012, Cincinnati, OH, 45229, USA.
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Kosheleva L, Koshelev D, Lagunas-Rangel FA, Levit S, Rabinovitch A, Schiöth HB. Disease-modifying pharmacological treatments of type 1 diabetes: Molecular mechanisms, target checkpoints, and possible combinatorial treatments. Pharmacol Rev 2025; 77:100044. [PMID: 40014914 PMCID: PMC11964952 DOI: 10.1016/j.pharmr.2025.100044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Accepted: 01/10/2025] [Indexed: 03/01/2025] Open
Abstract
After a century of extensive scientific investigations, there is still no curative or disease-modifying treatment available that can provide long-lasting remission for patients diagnosed with type 1 diabetes (T1D). Although T1D has historically been regarded as a classic autoimmune disorder targeting and destroying pancreatic islet β-cells, significant research has recently demonstrated that β-cells themselves also play a substantial role in the disease's progression, which could explain some of the unfavorable clinical outcomes. We offer a thorough review of scientific and clinical insights pertaining to molecular mechanisms behind pathogenesis and the different therapeutic interventions in T1D covering over 20 possible pharmaceutical intervention treatments. The interventions are categorized as immune therapies, treatments targeting islet endocrine dysfunctions, medications with dual modes of action in immune and islet endocrine cells, and combination treatments with a broader spectrum of activity. We suggest that these collective findings can provide a valuable platform to discover new combinatorial synergies in search of the curative disease-modifying intervention for T1D. SIGNIFICANCE STATEMENT: This research delves into the underlying causes of T1D and identifies critical mechanisms governing β-cell function in both healthy and diseased states. Thus, we identify specific pathways that could be manipulated by existing or new pharmacological interventions. These interventions fall into several categories: (1) immunomodifying therapies individually targeting immune cell processes, (2) interventions targeting β-cells, (3) compounds that act simultaneously on both immune cell and β-cell pathways, and (4) combinations of compounds simultaneously targeting immune and β-cell pathways.
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Affiliation(s)
- Liudmila Kosheleva
- Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Uppsala, Sweden
| | - Daniil Koshelev
- Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Uppsala, Sweden
| | - Francisco Alejandro Lagunas-Rangel
- Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Uppsala, Sweden; Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis, Riga, Latvia
| | - Shmuel Levit
- Diabetes and Metabolism Institute, Assuta Medical Centers, Tel Aviv, Israel
| | | | - Helgi B Schiöth
- Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Uppsala, Sweden; Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis, Riga, Latvia.
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Mohanty IR, Dhanawane U, Durgaprasad Tiwari D. Bio-standardization and development of a unique polyherbal formulation with dipeptidyl peptidase -IV inhibitory activity for type 2 diabetes mellitus. Nat Prod Res 2025:1-10. [PMID: 40022480 DOI: 10.1080/14786419.2025.2472283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 01/30/2025] [Accepted: 02/17/2025] [Indexed: 03/03/2025]
Abstract
Medicinal herbs may provide an alternative source of Dipeptidyl peptidase -IV (DPP-IV) Inhibitors, particularly in light of mounting evidence of high costs and adverse drug reactions associated with synthetic DPP-IV Inhibitors. DPP-IV inhibitory activity of medicinal plants Commiphora mukul, Terminalia arjuna and Phyllanthus emblica was elucidated in previous investigations from our lab. The goal of this work was to develop a polyherbal tablet including these medicinal plants with DPP-IV inhibitory action, conduct bio-standardization investigations, and test its anti-diabetic benefits in the streptozotocin model of Type 2 diabetes. A high-performance thin-layer chromatography technique was developed and validated in terms of linearity, accuracy, precision, repeatability, the limit of detection, and the limit of quantification for the bio-standardization of polyherbal combinations. Polyherbal combination's demonstrated significant DPP-IV inhibitory activity. It was interesting to note that in the Type II diabetes experimental model, the polyherbal combination showed antidiabetic efficacy equivalent to that of the synthetic DPP-IV inhibitor Vildagliptin, which is used in clinical settings.
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Affiliation(s)
| | - Ujwala Dhanawane
- Department of Pharmacology, MGM Medical College, Navi Mumbai, India
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Bhat KA, Singh KP, Maddukuri HR, Routray SN, Sharma S, Sharma SK, Patel K, Kinare V, Mate P, Lokesh Kumar RV. Clinical Profile, Comorbidities and Therapies in Type 2 Diabetes Patients on Sitagliptin-Based Therapy in Indian Outpatient Setting. Cureus 2024; 16:e74820. [PMID: 39737272 PMCID: PMC11684534 DOI: 10.7759/cureus.74820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/30/2024] [Indexed: 01/01/2025] Open
Abstract
Objectives The study was conducted to generate real-world data on prescription patterns and patient profiles for sitagliptin-based therapies in real-world outpatient settings across India. Method A cross-sectional, observational, multicenter, real-world prescription event monitoring (PEM) study was conducted at 1058 sites across India over six months, from 1 August 2023 to 16 January 2024. Adult type 2 diabetes patients receiving sitagliptin-based mono or combination therapies were included in the study. Primary outcomes assessed included the dosage of sitagliptin and other medications and the specific drugs combined with sitagliptin. Secondary outcomes included demographic profiles, medication history, comorbidities, and glycemic parameters. Results A total of 10210 patients (n=6398 males; n=3812 females) completed the study. Duration of diabetes was available for 5422 patients, of which nearly half of the patients had diabetes for 1-5 years, while around 42.3% (n=2294) of the patients had diabetes for more than five years. Comorbidities were present in 36.02% (n=3678) of the patients. Hypertension and dyslipidemia were the most common comorbidities reported in 25.3% (n=2584) and 10.42% (n=1064), respectively. Sitagliptin was administered as monotherapy or in combination with other medications. Dual combination therapy was most common, with sitagliptin 50 mg+metformin 500 mg being the predominantly prescribed regimen. Triple combination therapy with sitagliptin+dapagliflozin+metformin was also prescribed in a substantial proportion of the patients. Variations in preferred regimens were observed among patients with different comorbid conditions, with sitagliptin 100 mg+dapagliflozin 10 mg being preferred in patients with established cardiovascular disease and heart failure and sitagliptin 50 mg+metformin 500 mg in diabetic patients with hypertension, dyslipidemia, and renal disease. Conclusion The study findings highlighted the preferences for the use of sitagliptin and its dual as well as triple combinations as integral components of diabetes management strategies in clinical practice in Indian outpatient settings. The study also found that diabetes with ASCVD and CV risk factors influence the use of sitagliptin and dapagliflozin in combination.
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Affiliation(s)
| | - Kiran P Singh
- Diabetes and Endocrinology, Fortis Medcenter, Chandigarh, IND
| | | | - S N Routray
- Department of Cardiology, SCB Medical College and Hospital, Cuttack, IND
| | - Shreya Sharma
- Department of Endocrinology, Max Hospital, Dehradun, IND
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Santhakumar A, Lewis F, Pickles J, Winterbottom H, Punt S, Beynon J, Tofeec K, Barry P, Brennan A. Role for DPP4 inhibitor therapy in cystic fibrosis related diabetes: A single centre experience. J Cyst Fibros 2024; 23:853-856. [PMID: 38997826 DOI: 10.1016/j.jcf.2024.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Revised: 06/06/2024] [Accepted: 06/09/2024] [Indexed: 07/14/2024]
Abstract
INTRODUCTION Insulin remains the only recommended medical treatment for cystic fibrosis related diabetes (CFRD) Whilst there is an established role for orally bioavailable incretin mimetic agents such as the dipeptidyl peptidase-4 inhibitors (DPP4-I) in Type 2 diabetes mellitus, there exists little data on their utility in CFRD. AIM To examine the use of DPP4-I therapy in patients with CFRD at a single large adult cystic fibrosis center. METHOD People with CFRD prescribed a DPP4-I were identified from our specialist CFRD clinic and records were retrospectively examined for indication for therapy, tolerability and effectiveness. Analysis of continuous glucose monitoring data Libre 2 was done for these patients (CGM) pre and at least 3 months post therapy was performed. RESULTS 23 people with CF (PwCF) with a mean (SD) age of 35.0 ± 2.4 years were included in this analysis . In 21 patients DPP4-I was prescribed as a monotherapy and it was given in combination with insulin in 2 others. Indications for therapy included reactive hypoglycaemia (n = 10) post prandial hyperglycaemia (8), insulin avoidance (3), metformin intolerance (1) and unclear (1). Therapy was well tolerated with no discontinuations due to adverse effects. Significant improvements were noted in Time in Range- Pre vs Post: 78.0 [67.5 - 84.0] vs 89.0 [79.8 - 96.0]%, p = 0.005, Time above Range -Pre vs Post: 19.5 [12.5 - 30.8] vs 6.0 [2.5 - 16.5]%, p = 0.006 and glucose variability Pre versus Post: 28.3 [25.4 - 31.1] vs 26.9 [23.1 - 31.3], p = 0.021, Of the 10 subjects who initiated therapy for hypoglycaemia, 7 reported an improvement in symptoms. No significant difference was found in weight pre and post: 61.5 ± 15.0 kg vs 62.5 ± 15.3 kg, p = 0.326 or Hba1c pre vs post: 41.0 [36.0 - 53.3] mmol/mol versus 40.5 [36.8 - 47.3], p = 0.727. CONCLUSION DPP4-I is well tolerated in CFRD and can lead to an improved glycaemic control in these patients with significant improvement in validated CGM metrics.
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Affiliation(s)
- Anjali Santhakumar
- Manchester Adult Cystic Fibrosis Centre, Wythenshawe Hospital, Manchester University Hospital NHS Foundation Trust, United Kingdom; Department of Diabetes and Endocrinology, Wythenshawe Hospital, United Kingdom.
| | - Francine Lewis
- Manchester Adult Cystic Fibrosis Centre, Wythenshawe Hospital, Manchester University Hospital NHS Foundation Trust, United Kingdom
| | - Joanna Pickles
- Manchester Adult Cystic Fibrosis Centre, Wythenshawe Hospital, Manchester University Hospital NHS Foundation Trust, United Kingdom
| | - Hannah Winterbottom
- Manchester Adult Cystic Fibrosis Centre, Wythenshawe Hospital, Manchester University Hospital NHS Foundation Trust, United Kingdom
| | - Sam Punt
- Manchester Adult Cystic Fibrosis Centre, Wythenshawe Hospital, Manchester University Hospital NHS Foundation Trust, United Kingdom
| | - J Beynon
- Department of Diabetes and Endocrinology, Wythenshawe Hospital, United Kingdom
| | - K Tofeec
- Manchester Adult Cystic Fibrosis Centre, Wythenshawe Hospital, Manchester University Hospital NHS Foundation Trust, United Kingdom; Department of Diabetes and Endocrinology, Wythenshawe Hospital, United Kingdom
| | - P Barry
- Manchester Adult Cystic Fibrosis Centre, Wythenshawe Hospital, Manchester University Hospital NHS Foundation Trust, United Kingdom
| | - A Brennan
- Manchester Adult Cystic Fibrosis Centre, Wythenshawe Hospital, Manchester University Hospital NHS Foundation Trust, United Kingdom
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Guo L, Tian F, Liu L, Chen M, Jiang C, Li S, Liu C, Zhang Y, Qin J, Yu D, Zong Y, Dai W. Retagliptin as add-on therapy to metformin in Chinese patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Obes Metab 2024; 26:2830-2838. [PMID: 38602409 DOI: 10.1111/dom.15601] [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: 01/24/2024] [Revised: 03/27/2024] [Accepted: 03/27/2024] [Indexed: 04/12/2024]
Abstract
AIM To evaluate the efficacy and safety of retagliptin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin. MATERIALS AND METHODS This multicentre, phase 3 trial consisted of a 16-week, randomized, double-blind, placebo-controlled period, where patients with HbA1c levels between 7.5% and 11.0% were randomized to receive either once-daily (QD) retagliptin 100 mg (n = 87) or placebo (n = 87), both as an add-on to metformin. The primary endpoint was the change in HbA1c from baseline to week 16. RESULTS At week 16, the least squares mean change in HbA1c from baseline, compared with placebo, was -0.82% (95% CI, -1.05% to -0.58%) for the retagliptin 100 mg QD group (P < .0001) per treatment policy estimand. Significantly higher proportions of patients in the retagliptin 100 mg QD group achieved HbA1c levels of less than 6.5% (11.5%) and less than 7.0% (26.4%) compared with those receiving placebo (0% and 4.6%; P = .0016 and P < .0001, respectively) at week 16. Retagliptin 100 mg QD also lowered fasting plasma glucose and 2-hour postprandial plasma glucose levels. The incidence of adverse events (AEs) during the treatment period was similar between the two groups. However, slightly higher proportions of increased lipase and increased amylase in the retagliptin 100 mg QD group were observed. No patients discontinued treatment permanently because of AEs, and no episodes of severe hypoglycaemia were reported. CONCLUSIONS Retagliptin 100 mg QD as an add-on therapy to metformin offers a new therapeutic option for treating Chinese patients with T2D inadequately controlled by metformin alone, and is generally well tolerated.
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Affiliation(s)
- Lixin Guo
- Department of Endocrinology, Beijing Hospital; National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing, China
| | - Fengsheng Tian
- Department of Endocrinology, Hebei Province Cangzhou Hospital of Integrated Traditional Chinese Medicine-Western Medicine, Cangzhou, China
| | - Li Liu
- Department of Endocrinology, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Mingwei Chen
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Chengxia Jiang
- Department of Endocrinology, The Second People's Hospital of Yibin, Yibin, China
| | - Shuangqing Li
- Department of General practice, West China Hospital, Chengdu, China
| | - Cong Liu
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yawei Zhang
- Department of Endocrinology, Pingxiang People's Hospital, Pingxiang, China
| | - Jie Qin
- Department of Endocrinology, Shanxi Provincial People's Hospital, Taiyuan, China
| | - Dongni Yu
- Department of Endocrinology, Beijing Hospital; National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing, China
| | - Yicen Zong
- Clinical Research and Development, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China
| | - Wei Dai
- Clinical Research and Development, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China
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Conroy LJ, McCann A, Zhang N, de Gaetano M. The role of nanosystems in the delivery of glucose-lowering drugs for the preemption and treatment of diabetes-associated atherosclerosis. Am J Physiol Cell Physiol 2024; 326:C1398-C1409. [PMID: 38525540 DOI: 10.1152/ajpcell.00695.2023] [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: 12/14/2023] [Revised: 03/19/2024] [Accepted: 03/19/2024] [Indexed: 03/26/2024]
Abstract
Diabetes is one of the most prevalent diseases worldwide. In recent decades, type-2 diabetes has become increasingly common, particularly in younger individuals. Diabetes leads to many vascular complications, including atherosclerosis. Atherosclerosis is a cardiovascular disease characterized by lipid-rich plaques within the vasculature. Plaques develop over time, restricting blood flow, and can, therefore, be the underlying cause of major adverse cardiovascular events, including myocardial infarction and stroke. Diabetes and atherosclerosis are intrinsically linked. Diabetes is a metabolic syndrome that accelerates atherosclerosis and increases the risk of developing other comorbidities, such as diabetes-associated atherosclerosis (DAA). Gold standard antidiabetic medications focus on attenuating hyperglycemia. Though recent evidence suggests that glucose-lowering drugs may have broader applications, beyond diabetes management. This review mainly evaluates the role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as liraglutide and semaglutide in DAA. These drugs mimic gut hormones (incretins), which inhibit glucagon secretion while stimulating insulin secretion, thus improving insulin sensitivity. This facilitates delayed gastric emptying and increased patient satiety; hence, they are also indicated for the treatment of obesity. GLP-1 RAs have significant cardioprotective effects, including decreasing low-density lipoprotein (LDL) cholesterol and triglycerides levels. Liraglutide and semaglutide have specifically been shown to decrease cardiovascular risk. Liraglutide has displayed a myriad of antiatherosclerotic properties, with the potential to induce plaque regression. This review aims to address how glucose-lowering medications can be applied to treat diseases other than diabetes. We specifically focus on how nanomedicines can be used for the site-specific delivery of antidiabetic medicines for the treatment of diabetes-associated atherosclerosis.
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Affiliation(s)
- Luke James Conroy
- Diabetes Complications Research Centre, Conway Institute & School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
| | - Alyssa McCann
- School of Mechanical and Materials Engineering, University College Dublin, Dublin, Ireland
| | - Nan Zhang
- School of Mechanical and Materials Engineering, University College Dublin, Dublin, Ireland
| | - Monica de Gaetano
- Diabetes Complications Research Centre, Conway Institute & School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
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Sivaraman SA, Sabareesh V. An Update on Dipeptidyl Peptidase-IV Inhibiting Peptides. Curr Protein Pept Sci 2024; 25:267-285. [PMID: 38173201 DOI: 10.2174/0113892037287976231212104607] [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: 10/21/2023] [Revised: 11/30/2023] [Accepted: 12/05/2023] [Indexed: 01/05/2024]
Abstract
Diabetes is a chronic metabolic disorder. According to the International Diabetes Federation, about 537 million people are living with diabetes. The two types of diabetes are type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), among which the population affected by T2DM is relatively higher. A major reason for T2DM is that insulin stimulation is hampered due to the inactivation of incretin hormones. Dipeptidyl peptidase-IV (DPP-IV) is a serine protease that is directly involved in the inactivation of incretin hormones, e.g., glucagon-like peptide-1 (GLP-1). Therefore, the inhibition of DPP-IV can be a promising method for managing T2DM, in addition to other enzyme inhibition strategies, such as inhibition of α-amylase and α -glucosidase. Currently, about 12 different gliptin drugs are available in the market that inhibit DPP-IV in a dose-dependent manner. Instead of gliptins, 'peptides' can also be employed as an alternative and promising way to inhibit DPP-IV. Peptide inhibitors of DPP-IV have been identified from various plants and animals. Chemically synthesized peptides have also been experimented for inhibiting DPP-IV. Most peptides have been analysed by biochemical assays, whereas some in vitro assays have also been reported. Molecular docking analysis has been applied to comprehend the mechanism of inhibition. In this review, certain aspects of natural as well as synthetic peptides are described that have been proven to inhibit DPP-IV.
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Affiliation(s)
- Sachithanantham Annapoorani Sivaraman
- Centre for Bio-Separation Technology (CBST), Vellore Institute of Technology (VIT), Vellore, Tamil Nadu 632 014, India
- School of Bio Sciences and Technology (SBST), Vellore Institute of Technology (VIT), Vellore, Tamil Nadu 632 014, India
| | - Varatharajan Sabareesh
- Centre for Bio-Separation Technology (CBST), Vellore Institute of Technology (VIT), Vellore, Tamil Nadu 632 014, India
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Singh H, Rohilla R, Jaswal S, Singla M. Comparison of teneligliptin and other gliptin-based regimens in addressing insulin resistance and glycemic control in type 2 diabetic patients: a cross-sectional study. Expert Rev Endocrinol Metab 2024; 19:81-87. [PMID: 38078453 DOI: 10.1080/17446651.2023.2290486] [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: 08/30/2023] [Accepted: 11/02/2023] [Indexed: 01/03/2024]
Abstract
INTRODUCTION The objective of this study was to compare the effects of teneligliptin-based regimens and other gliptin-based regimens with respect to insulin resistance and glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS We enrolled T2DM subjects, inadequately controlled with metformin and glimepiride and taking one of the gliptins, and divided them into two groups, i.e. group 1 (teneligliptin-based regimens) and group 2 (other gliptin-based regimens). Fasting plasma insulin, adiponectin levels, homeostatic model assessment for insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), and fasting blood glucose (FBG) were measured and compared. Costs of different gliptins were noted, and mean cost of per day therapy was compared. RESULTS Eighty-six subjects participated in this study (43 each in group 1 and group 2). No significant differences were observed in FBG, HbA1c, insulin levels, and HOMA-IR, but the trend was in favor of teneligliptin-based regimens. A significantly higher number of subjects achieved HbA1c target in group 1 (P < 0.001). Teneligliptin had significantly lower cost of per day therapy as compared to other dipeptidyl peptidase-4 inhibitors. CONCLUSION Teneligliptin seems to be cost-effective and safer option in T2DM subjects who were not adequately controlled with metformin and sulfonylureas. However, further prospective studies are needed.
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Affiliation(s)
- Harmanjit Singh
- Department of Pharmacology, Government Medical College & Hospital, Chandigarh, India
| | - Ravi Rohilla
- Department of Community Medicine, Government Medical College & Hospital, Chandigarh, India
| | - Shivani Jaswal
- Department of Biochemistry, Government Medical College & Hospital, Chandigarh, India
| | - Mandeep Singla
- Department of General Medicine, Government Medical College & Hospital, Chandigarh, India
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Tschöp MH, Friedman JM. Seeking satiety: From signals to solutions. Sci Transl Med 2023; 15:eadh4453. [PMID: 37992155 DOI: 10.1126/scitranslmed.adh4453] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Accepted: 11/03/2023] [Indexed: 11/24/2023]
Abstract
Remedies for the treatment of obesity date to Hippocrates, when patients with obesity were directed to "reduce food and avoid drinking to fullness" and begin "running during the night." Similar recommendations have been repeated ever since, despite the fact that they are largely ineffective. Recently, highly effective therapeutics were developed that may soon enable physicians to manage body weight in patients with obesity in a manner similar to the way that blood pressure is controlled in patients with hypertension. These medicines have grown out of a revolution in our understanding of the molecular and neural control of appetite and body weight, reviewed here.
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Affiliation(s)
- Matthias H Tschöp
- Helmholtz Munich and Technical University Munich, Munich, 85758 Germany
| | - Jeffrey M Friedman
- Laboratory of Molecular Genetics, Howard Hughes Medical Institute, Rockefeller University, New York, NY 10065 USA
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Khan A, Kanpurwala MA, Khan RA, Mahmudi NF, Lohano V, Ahmed S, Khan M, Uddin F, Ali SM, Saghir M, Baqar Abidi SH, Kamal J. Impact of Treviamet® & Treviamet XR® on quality of life besides glycemic control in type 2 DM patients. BMC Endocr Disord 2023; 23:244. [PMID: 37940936 PMCID: PMC10631090 DOI: 10.1186/s12902-023-01492-2] [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: 08/09/2023] [Accepted: 10/17/2023] [Indexed: 11/10/2023] Open
Abstract
BACKGROUND Maintaining the quality of life is the main objective of managing type 2 diabetes (T2DM) (QoL). Since it is a key factor in patient motivation and adherence, treatment-related QoL has always been considered when choosing glucose-lowering medicines. The objective of the study was to evaluate the quality of life besides glycemic control among type 2 diabetes mellitus patients receiving Treviamet® & Treviamet XR® (Sitagliptin with Metformin) in routine care. METHODS It was a prospective, open-label, non-randomized clinical trial including T2DM patients uncontrolled on Metformin therapy. All patients received Treviamet® & Treviamet XR® for six months. Sequential changes in QoL, fasting plasma glucose, HbA1c, body weight, and blood pressure were monitored from baseline to 3 consecutive follow-up visits. The frequency of adverse events (AEs) was also noted throughout the study. RESULTS A total of 504 patients were screened; 188 completed all three follow-ups. The mean QoL score significantly declined from 57.09% at baseline to 33.64% at the 3rd follow-up visit (p < 0.01). Moreover, a significant decline in mean HbA1c and FPG levels was observed from baseline to 3rd follow-up visit (p < 0.01). Minor adverse events were observed, including abdominal discomfort, nausea, flatulence, and indigestion. Gender, HbA1c, diarrhea, and abdominal discomfort were significant predictors of a patient's QoL, as revealed by the Linear Regression Model (R2 = 0.265, F(16, 99) = 2.231). CONCLUSION Treviamet® & Treviamet XR® significantly improved glycemic control (HbA1c levels) and QoL in T2DM patients without serious adverse events. TRIAL REGISTRATION ClinicalTrials.gov identifier (NCT05167513), Date of registration: December 22, 2021.
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Affiliation(s)
- Asima Khan
- Public Health Department, Baqai Institute of Diabetology and Endocrinology, Karachi, Pakistan
| | - Muhammad Adnan Kanpurwala
- Department of Physiology, Karachi Institute of Medical Sciences affiliated with NUMS, Karachi, Pakistan.
| | - Riasat Ali Khan
- Diabetes, Baqai Institute of Diabetology and Endocrinology, Karachi, Pakistan
| | | | | | - Shakeel Ahmed
- Diabetes & Endocrinology Department, College of Family Medicine, Karachi, Pakistan
| | - Majid Khan
- Memon Medical Complex, Karachi, Pakistan
| | | | | | | | | | - Jahanzeb Kamal
- Medical Education, College of Physicians and Surgeons Pakistan, Karachi, Pakistan
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12
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Hong JH, Moon JS, Seong K, Lim S. Comparison of therapeutic efficacy and safety of sitagliptin, dapagliflozin, or lobeglitazone adjunct therapy in patients with type 2 diabetes mellitus inadequately controlled on sulfonylurea and metformin: Third agent study. Diabetes Res Clin Pract 2023; 203:110872. [PMID: 37574137 DOI: 10.1016/j.diabres.2023.110872] [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: 06/03/2023] [Revised: 08/07/2023] [Accepted: 08/10/2023] [Indexed: 08/15/2023]
Abstract
AIMS Compare the efficacy and safety of sitagliptin, dapagliflozin, and lobeglitazone in patients with uncontrolled type 2 diabetes, despite metformin and sulfonylurea therapy. METHODS The study randomized patients into three groups, receiving sitagliptin 100 mg, dapagliflozin 10 mg, or lobeglitazone 0.5 mg daily (n = 26 each) and monitored changes in biochemical parameters and body composition for 24 months. The primary efficacy endpoint was changes in HbA1c at 24 months. RESULTS The mean change in HbA1c in the sitagliptin, dapagliflozin, and lobeglitazone groups was -0.81 ± 0.21%, -1.05 ± 0.70%, and -1.08 ± 0.98%, after 24 months. Dapagliflozin treatment significantly lowered systolic blood pressure by 5.5 mmHg and alanine aminotransferase levels. Dapagliflozin and lobeglitazone treatment significantly reduced proteinuria and insulin resistance. Dapagliflozin decreased whole body fat percentage by 1.2%, whereas sitagliptin and lobeglitazone increased it by 1.1% and 1.8%, respectively. Whole body muscle percentage increased in the dapagliflozin group and decreased in the lobeglitazone group. The safety profiles of the three treatments were comparable. CONCLUSIONS All three drugs displayed good glucose-lowering efficacy and comparable safety profiles. However, dapagliflozin therapy produced favorable changes in body composition. Dapagliflozin may be a suitable adjunct therapy for patients with type 2 diabetes seeking to improve their body composition.
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Affiliation(s)
- Jun Hwa Hong
- Department of Internal Medicine, Daejeon Eulji Medical Center, Eulji University, Daejeon, Republic of Korea.
| | - Jun Sung Moon
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Republic of Korea.
| | - Kayeon Seong
- Department of Internal Medicine, Daejeon Eulji Medical Center, Eulji University, Daejeon, Republic of Korea.
| | - Soo Lim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
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Reghunath SR, Rashid M, Chandran VP, Thunga G, Shivashankar KN, Acharya LD. Factors contributing to the adverse drug reactions associated with the dipeptidyl peptidase-4 (DPP-4) inhibitors: A scoping review. Diabetes Metab Syndr 2023; 17:102790. [PMID: 37329838 DOI: 10.1016/j.dsx.2023.102790] [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: 09/09/2022] [Revised: 01/30/2023] [Accepted: 05/24/2023] [Indexed: 06/19/2023]
Abstract
BACKGROUND AND AIM Adverse drug reactions are one of the contributors to increased hospital admission and length of hospital stay. Among the various antidiabetic agents prescribed, dipeptidyl peptidase-4 (DPP-4) inhibitors have gained wide recognition and shown more persistence than other novel hypoglycemic agents. We performed a scoping review to identify the risk factors contributing to the adverse drug reactions with DPP-4 inhibitors. METHODOLOGY We followed Preferred Reporting Items for Scoping Review (PRISMA-ScR) Guidelines for reporting the findings. Data sources such as PubMed/MEDLINE, Scopus, Embase, and Cochrane were assessed. We included studies that reported the risk factors contributing to the DPP-4 inhibitor-associated adverse drug reactions. The Joanna Briggs Institute (JBI) critical appraisal checklist was used to assess the methodological quality of the studies. RESULTS Of the 6406 studies retrieved, 11 studies met our inclusion criteria. Of these 11 studies, seven were post-marketing surveillance studies, one nested case-control study, one comparator cohort study, one food and drug administration (FDA) adverse event reporting system (FAERS)-based observational study, and one questionnaire-based cross-sectional survey study. A total of eight factors were identified that contributed to the DPP-4 inhibitor-associated adverse drug reactions. CONCLUSION The included studies suggested age >65 years, females, grade 4 and 5 renal impairment, concomitant drugs, disease and drug therapy duration, liver disease, non-smokers, and non-hypertension as risk factors. Further studies should be conducted to provide insight into these risk factors so that the appropriate use of DPP-4 inhibitors in the diabetic population can be encouraged to improve the health-related quality of life. PROSPERO REGISTRATION CRD42022308764.
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Affiliation(s)
- Swetha R Reghunath
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Udupi District, Karnataka, 576 104, India.
| | - Muhammed Rashid
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Udupi District, Karnataka, 576 104, India.
| | - Viji Pulikkel Chandran
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Udupi District, Karnataka, 576 104, India.
| | - Girish Thunga
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Udupi District, Karnataka, 576 104, India.
| | - K N Shivashankar
- Department of General Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Udupi District, Karnataka, 576 104, India.
| | - Leelavathi D Acharya
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Udupi District, Karnataka, 576 104, India.
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Pelluri R, Kongara S, Nagasubramanian VR, Mahadevan S, Chimakurthy J. Systematic review and meta-analysis of teneligliptin for treatment of type 2 diabetes. J Endocrinol Invest 2023; 46:855-867. [PMID: 36624224 DOI: 10.1007/s40618-023-02003-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 12/31/2022] [Indexed: 01/11/2023]
Abstract
BACKGROUND AND AIM There are efficacy and safety concerns related to teneligliptin treatment. A systematic review of randomized controlled trials (RCTs) was undertaken to comprehensively profile the efficacy and safety of teneligliptin in the treatment of type 2 diabetes mellitus (T2DM). METHODS Thirteen studies were chosen from a search of scientific databases for RCTs using teneligliptin as a monotherapy or as an adjunct to other glycemic agents with pre-specified inclusion criteria. We calculated weighted mean differences (WMDs) and 95% confidence intervals (CIs) in each included trial and pooled the data using a random-effects model. RESULTS Thirteen studies enrolled 2853 patients were identified. Teneligliptin treatment was associated with weight gain (vs. placebo, weighted mean difference (WMD) 0.28 kg; 95% CI - 0.20-0.77 kg; I2 = 86%; P = 0.25). Compared to monotherapy, add on therapy with teneligliptin showed significant improvement in FPG mg/dl levels (WMD - 16.75 mg/dl; 95% CI - 19.38 to - 14.13 mg/dl), HOMA-β (WMD 7.91; 95% CI 5.38-10.45) and HOMA-IR (WMD - 0.27; 95% CI - 0.46 to - 0.07). The improvement in HbA1c was greater with monotherapy (WMD - 8.88 mmol/mol; 95% CI - 9.59 to - 8.08 mmol/mol). There was no significant risk of any hypoglycemia with teneligliptin compared to placebo (OR 0.84; 95% CI 0.44-1.60; I2 = 0%; P = 0.60). However, the risk was 1.84 times high when combined with other glycemic agents. The risk of cardiovascular events was comparable, regardless of treatment duration when compared to placebo or any other active comparator (OR 0.79; 95% CI 0.40-1.57; I2 = 0%; P = 0.50). [PROSPERO, CRD42022360785]. CONCLUSIONS Teneligliptin is an effective and safe therapeutic option for patients with T2DM, both as monotherapy and as add-on therapy. However, additional large-scale, high-quality, long-term follow-up clinical trials with diverse ethnic populations are required to confirm its long-term efficacy and safety.
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Affiliation(s)
- R Pelluri
- Department of Pharmacy Practice, Vignan Pharmacy College, Guntur, 522213, India
- Department of Endocrinology and Metabolism, Endo-Life Speciality Hospital, Guntur, 522001, India
- Department of Pharmacy Practice, Sri Ramachandra Institute of Higher Education Research, (Deemed to be University), Porur, Chennai, 600116, India
| | - S Kongara
- Department of Endocrinology and Metabolism, Endo-Life Speciality Hospital, Guntur, 522001, India.
| | - V R Nagasubramanian
- Department of Pharmacy Practice, Sri Ramachandra Institute of Higher Education Research, (Deemed to be University), Porur, Chennai, 600116, India.
| | - S Mahadevan
- Department of Endocrinology and Metabolism, Sri Ramachandra Institute of Higher Education and Research, (Deemed to Be University), Porur, Chennai, 600116, India
| | - J Chimakurthy
- Department of Pharmaceutical Sciences, Vignan's Foundation for Science Technology and Research, (Deemed to Be University), Guntur, 522213, India
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Zhu J, Han J, Liu L, Liu Y, Xu W, Li X, Yang L, Gu Y, Tang W, Shi Y, Ye S, Hua F, Xiang G, Liu M, Sun Z, Su Q, Li X, Li Y, Li Y, Li H, Li Y, Yang T, Yang J, Shi L, Yu X, Chen L, Shao J, Liang J, Han X, Xue Y, Ma J, Zhu D, Mu Y. Clinical expert consensus on the assessment and protection of pancreatic islet β-cell function in type 2 diabetes mellitus. Diabetes Res Clin Pract 2023; 197:110568. [PMID: 36738836 DOI: 10.1016/j.diabres.2023.110568] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 01/08/2023] [Accepted: 01/30/2023] [Indexed: 02/05/2023]
Abstract
Islet β-cell dysfunction is a basic pathophysiological characteristic of type 2 diabetes mellitus (T2DM). Appropriate assessment of islet β-cell function is beneficial to better management of T2DM. Protecting islet β-cell function is vital to delay the progress of type 2 diabetes mellitus. Therefore, the Pancreatic Islet β-cell Expert Panel of the Chinese Diabetes Society and Endocrinology Society of Jiangsu Medical Association organized experts to draft the "Clinical expert consensus on the assessment and protection of pancreatic islet β-cell function in type 2 diabetes mellitus." This consensus suggests that β-cell function can be clinically assessed using blood glucose-based methods or methods that combine blood glucose and endogenous insulin or C-peptide levels. Some measures, including weight loss and early and sustained euglycemia control, could effectively protect islet β-cell function, and some newly developed drugs, such as Sodium-glucose cotransporter-2 inhibitor and Glucagon-like peptide-1 receptor agonists, could improve islet β-cell function, independent of glycemic control.
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Affiliation(s)
- Jian Zhu
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Junfeng Han
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China
| | - Liehua Liu
- Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yu Liu
- Endocrinology Department, Sir Run Run Hospital of Nanjing Medical University, Nanjing, China
| | - Wen Xu
- Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Diabetology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiaomu Li
- Department of Endocrine and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Lin Yang
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Yong Gu
- Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wei Tang
- Department of Endocrinology, Geriatric Hospital of Nanjing Medical University, Nanjing, China
| | - Yongquan Shi
- Department of Endocrinology, Changzheng Hospital, The Navy Military Medical University, Shanghai, China
| | - Shandong Ye
- Department of Endocrinology, Anhui Provincial Hospital, Hefei, China
| | - Fei Hua
- Department of Endocrinology, The First People's Hospital of Changzhou, Changzhou, China
| | - Guangda Xiang
- Department of Endocrinology, General Hospital of Central Theater Command of Chinese People' s Liberation Army, Wuhan, China
| | - Ming Liu
- Department of Endocrinology, General Hospital, Tianjin Medical University, Tianjin, China
| | - Zilin Sun
- Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, China
| | - Qing Su
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Xiaoying Li
- Department of Endocrine and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yuxiu Li
- Department of Endocrinology, Peking Union Medical College Hospital, Beijing, China
| | - Yanbing Li
- Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Hong Li
- Department of Endocrinology, First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yiming Li
- Department of Endocrinology, Huashan Hospital, Fudan University, Shanghai, China
| | - Tao Yang
- Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jing Yang
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Lixin Shi
- Department of Endocrinology, Guiqian International General Hospital, Guiyang 550018, China
| | - Xuefeng Yu
- Department of Endocrinology, Tongji Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan, China
| | - Li Chen
- Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, China
| | - Jiaqing Shao
- Department of Endocrinology, the Affiliated Jinling Hospital of Nanjing Medical University, General Hospital of Eastern Theater Command, Nanjing, China
| | - Jun Liang
- Department of Endocrinology, Xuzhou Central Hospital, Xuzhou, China
| | - Xiao Han
- Key Laboratory of Human Functional Genomics of Jiangsu Province, School of Basic Medical Science, Nanjing Medical University, Nanjing, China
| | - Yaomin Xue
- The First Clinical Medical Institute, Southern Medical University, Guangzhou, China
| | - Jianhua Ma
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
| | - Dalong Zhu
- Department of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, China.
| | - Yiming Mu
- Department of Endocrinology, Chinese PLA General Hospital, Beijing, China.
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16
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Yardstick for managing cough, part 1: In adults and adolescent patients older than 14 years of age. Ann Allergy Asthma Immunol 2023; 130:379-391. [PMID: 36526233 DOI: 10.1016/j.anai.2022.12.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 12/02/2022] [Accepted: 12/05/2022] [Indexed: 12/14/2022]
Abstract
Nationwide statistics in the United States and Australia reveal that cough of undifferentiated duration is the most common complaint for which patients of all ages seek medical care in the ambulatory setting. Management of chronic cough is one of the most common reasons for new patient visits to pulmonologists. Because symptomatic cough is such a common problem and so much has been learned about how to diagnose and treat cough of all durations but especially chronic cough, this 2-part yardstick has been written to review in a practical way the latest evidence-based guidelines most of which have been developed from recent high quality systematic reviews on how best to manage cough of all durations in adults, adolescents, and children. In this manuscript, part 1 of the 2-part series, we provide evidence-based, and expert opinion recommendations on the management of chronic cough in adult and adolescent patients (>14 years of age).
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Schnaars Y, Gaikwad S, Gottwald-Hostalek U, Uhl W, Ribot O, Varanasi KVS, Rodríguez L, Torrejón J, Gómez L. Bioequivalence Evaluation in Healthy Volunteers: New Generic Formulations of Sitagliptin and Sitagliptin-Metformin Fixed-Dose Combination Compared with the Originator Products. Diabetes Ther 2023; 14:347-362. [PMID: 36526947 PMCID: PMC9943811 DOI: 10.1007/s13300-022-01349-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 11/24/2022] [Indexed: 12/23/2022] Open
Abstract
INTRODUCTION Three studies compared the bioequivalence (BE) of new generic tablet formulations of sitagliptin (100 mg; fasting) and the fixed-dose combination (FDC) of sitagliptin/metformin (50/850 mg, 50/1000 mg; both fed) in healthy volunteers with the same tablet strengths of the reference products Januvia and Janumet. METHODS The study design was open-label, single-dose, randomized with two-way crossover periods. Blood sampling was performed for 72/48 h in the sitagliptin/FDC studies, respectively. Primary pharmacokinetic (PK) parameters for sitagliptin and metformin were area under the plasma concentration-time curve from time 0 to last timepoint of measurable concentration (AUC0-t) and maximum plasma concentration (Cmax). Test (T) and reference (R) formulations proved bioequivalent if 90% confidence interval (CI) of geometric least-squares mean ratio for AUC0-t and Cmax were within BE acceptance range of 80.00-125.00%. Safety evaluations included vital signs, clinical laboratory tests, and adverse events (AEs). RESULTS Treated/evaluable volunteers for BE per study were: 30/28 (sitagliptin 100 mg), 26/25 (FDC 50/850 mg), and 26/24 (FDC 50/1000 mg). The 90% CI of the geometric means of T/R ratios for primary PK parameters were within predefined BE limits: CI for AUC0-t and Cmax were 95.83-100.37% and 91.85-109.56% (sitagliptin 100 mg); 100.84-103.69% and 93.44-105.10% (FDC 50/850 mg), and 101.26-105.20% and 98.71-112.89% (FDC 50/1000 mg); respective values for metformin were 94.23-101.89% and 91.66-99.38% (FDC 50/850 mg) and 98.45-104.89% and 96.79-105.62% (FDC 50/1000 mg). All AEs were nonserious, transient, and mostly mild. Safety evaluations did not reveal any relevant difference between T and R formulations. CONCLUSIONS The new generic tablet formulations of sitagliptin 100 mg and the FDCs sitagliptin/metformin 50/850 mg and 50/1000 mg demonstrated bioequivalence to originator reference products. Therefore, the new products are expected to provide efficacy and tolerability similar to those of the reference products in the treatment of patients with type 2 diabetes (T2D). TRIAL REGISTRATION EudraCT EU Clinical Trials Registry (2014-005437-31); ClinicalTrials.gov Registry (NCT05549570 and NCT05549583, both retrospectively registered on 20 September 2022).
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Affiliation(s)
- Yvonne Schnaars
- Merck Healthcare KGaA, Frankfurter Str. 250, Post Code F135 /001, 64293, Darmstadt, Germany.
| | - Sumedh Gaikwad
- Merck Healthcare KGaA, Frankfurter Str. 250, Post Code F135 /001, 64293, Darmstadt, Germany
| | | | - Wolfgang Uhl
- Merck Healthcare KGaA, Frankfurter Str. 250, Post Code F135 /001, 64293, Darmstadt, Germany
| | - Olga Ribot
- Galenicum Health S.L.U., Barcelona, Spain
| | | | | | | | - Luis Gómez
- Galenicum Health S.L.U., Barcelona, Spain
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Nagao M, Sasaki J, Sugihara H, Tanimura-Inagaki K, Harada T, Sakuma I, Oikawa S. Efficacy and safety of sitagliptin treatment in older adults with moderately controlled type 2 diabetes: the STREAM study. Sci Rep 2023; 13:134. [PMID: 36599895 DOI: 10.1038/s41598-022-27301-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 12/29/2022] [Indexed: 01/06/2023] Open
Abstract
Sitagliptin has been suggested as a treatment option for older adults with type 2 diabetes (T2D). However, no randomized controlled trial has been performed to evaluate the efficacy and safety of sitagliptin treatment in older Japanese patients with T2D. The STREAM study was a multicenter, open-label, randomized controlled trial. T2D outpatients aged 65-80 years with moderately controlled glycemic levels (HbA1c 7.4-10.4%) under lifestyle interventions without or with oral anti-diabetic drugs excluding DPP4 inhibitors or GLP-1 receptor agonists were recruited (n = 176). The participants were randomized into sitagliptin group (n = 88) who received sitagliptin as an initial or an additive anti-diabetic drug and control group (n = 88) who did not. The treatment goal was HbA1c level < 7.4%. Efficacy and safety during 12-month treatment period were investigated. The mean (± SD) ages were 70.6 ± 3.9 and 71.9 ± 4.4 years old in sitagliptin and control groups, respectively. According to a mixed-effects model analysis, average changes from baseline over the treatment period in fasting plasma glucose (FPG), HbA1c, and glycated albumin (GA) were - 27.2 mg/dL, - 0.61%, and - 2.39%, respectively, in sitagliptin group, and 0.50 mg/dL, - 0.29%, and - 0.93%, respectively, in control group. The reductions in FPG, HbA1c, and GA were significantly greater in sitagliptin group (P < 0.0001, P < 0.01, and P < 0.0001, respectively). There were no differences in the incidence of adverse effects, except for cystatin C elevation and platelet count reduction in sitagliptin group. Sitagliptin treatment effectively improved the glycemic profile without any serious adverse effects in older T2D patients.Trial registration number: UMIN000010376.
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Affiliation(s)
- Mototsugu Nagao
- Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Jun Sasaki
- International University of Health and Welfare, Fukuoka, Japan
| | - Hitoshi Sugihara
- Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Kyoko Tanimura-Inagaki
- Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Taro Harada
- Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Ichiro Sakuma
- Caress Sapporo Hokko Memorial Clinic, Hokkaido, Japan
| | - Shinichi Oikawa
- Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. .,Diabetes and Lifestyle-Related Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association (JATA), 3-1-24 Matsuyama, Kiyose, Tokyo, 204-8522, Japan.
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Que L, Qin W, Shi Y, Ding Y, Huang K, Qian Z, Huang B, Zhou P, He Q. Pharmacokinetic comparison of sitagliptin and metformin HCl extended-release tablets versus JANUMET ® XR in healthy volunteers under fasting and fed conditions. Front Pharmacol 2023; 14:1105767. [PMID: 37033652 PMCID: PMC10073488 DOI: 10.3389/fphar.2023.1105767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Accepted: 03/13/2023] [Indexed: 04/11/2023] Open
Abstract
Background and Objectives: Janumet® XR is the combination of sitagliptin and extended metformin hydrochloride produced by Merck Sharp & Dohme. It is specially designed for diabetes mellitus patients taking both drugs already. Janumet® XR exhibited clinically significant blood glucose lowering efficacy and long-term use safety. However, no generic form of Janumet® XR has been approved in western countries. The relatively high cost made the medication less prescribed. A more affordable form of this drug may benefit an immense diabetes mellitus population. The current study compared the bioequivalence (BE) of sitagliptin 100 mg and metformin 1000 mg produced by Nanjing Chia-Tai Tianqing Pharmaceutical Company to Janumet® XR in healthy Chinese subjects. Methods: Twenty-eight healthy Chinese subjects were enrolled in Study 1 and 2, respectively. Both studies were conducted with an open, randomized, two-period crossover design using the test (T) or the reference (R) drug. Study 1 is conducted under the fasting state, and Study 2 is under the fed state. Subjects received an oral dose of sitagliptin 100 mg and metformin 1000 mg, and plasma concentrations of sitagliptin and metformin were determined up to 72 h post-dose. Pharmacokinetic (PK) parameters, including maximum serum concentration (Cmax) and area under the concentration-time curve up to the last quantifiable concentration (AUC0-t) of both sitagliptin and metformin, were calculated and compared between the T and R treatments. Results: In the fasting study, the geometric mean ratios of Cmax, AUC0-t, and AUC0-∞ for sitagliptin were 109.42%, 101.93%, and 101.95%, respectively; the corresponding ratios for metformin were 98.69%, 94.12%, and 93.42%, respectively. In the fed study, the geometric mean ratios of Cmax, AUC0-t, and AUC0-∞ for sitagliptin were 98.41%, 100.30%, and 100.24%, respectively; the corresponding ratios for metformin were 97.79%, 99.28%, and 100.69%, respectively. The 90% CIs of Cmax, AUC0-t, and AUC0-∞ in both studies were all within acceptance limits (80.00%-125.00%). Conclusion: The results demonstrated for the first time that sitagliptin 100 mg and metformin 1000 mg produced by Nanjing Chia-Tai Tianqing Pharmaceutical Company was bioequivalent to the branded Janumet® XR, and both drugs were well tolerated.
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Affiliation(s)
- Linling Que
- Drug Clinical Trial Institution, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
| | - Wei Qin
- Drug Clinical Trial Institution, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
| | - Yunfei Shi
- Drug Clinical Trial Institution, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
| | - Ying Ding
- Drug Clinical Trial Institution, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
| | - Kai Huang
- Drug Clinical Trial Institution, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
| | - Zhenzhong Qian
- Drug Clinical Trial Institution, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
| | - Bingjie Huang
- Nanjing Chia-Tai Tianqing Pharmaceutical Company, Nanjing, China
| | - Peipei Zhou
- Nanjing Chia-Tai Tianqing Pharmaceutical Company, Nanjing, China
| | - Qing He
- Drug Clinical Trial Institution, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
- *Correspondence: Qing He,
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Xu J, Ling H, Geng J, Huang Y, Xie Y, Zheng H, Niu H, Zhang T, Yuan J, Xiao X. Efficacy and safety of DBPR108 (prusogliptin) as an add-on to metformin therapy in patients with type 2 diabetes: A 24-week, multi-centre, randomized, double-blind, placebo-controlled, superiority, phase III clinical trial. Diabetes Obes Metab 2022; 24:2232-2240. [PMID: 35791646 PMCID: PMC9796963 DOI: 10.1111/dom.14810] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 06/24/2022] [Accepted: 07/01/2022] [Indexed: 01/07/2023]
Abstract
AIM To evaluate the efficacy and safety of DBPR108 (prusogliptin), a novel dipeptidyl peptidase-4 (DPP-4) inhibitor, as an add-on therapy in patients with type 2 diabetes (T2D) that is inadequately controlled with metformin. MATERIALS AND METHODS In this 24-week, multi-centre, randomized, double-blind, placebo-controlled, superiority, phase III study, adult T2D patients with HbA1c levels ranging from 7.0% to 9.5% on stable metformin were enrolled and randomized (2:1) into the DBPR108 + metformin and placebo + metformin groups. The primary endpoint was the change from baseline in HbA1c at week 24 of DBPR108 versus placebo as an add-on therapy to metformin. RESULTS At week 24, the least-square mean (standard error) change from baseline in HbA1c was significantly greater in the DBPR108 group (-0.70% [0.09%]) than in the placebo group (-0.07% [0.11%]) (P < .001), with a treatment difference of -0.63% (95% confidence interval: -0.87%, -0.39%) on the full analysis set. A higher proportion of patients achieved an HbA1c of 6.5% or less (19.7% vs. 8.5%) and an HbA1c of 7.0% or less (50.0% vs. 21.1%) at week 24 in the DBPR108 + metformin group. Furthermore, add-on DBPR108 produced greater reductions from baseline in fasting plasma glucose and 2-hour postprandial plasma glucose without causing weight gain. The overall frequency of adverse events was similar between the two groups. CONCLUSIONS DBPR108 as add-on therapy to metformin offered a significant improvement in glycaemic control, was superior to metformin monotherapy (placebo) and was safe and well-tolerated in patients with T2D that is inadequately controlled with metformin.
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Affiliation(s)
- Jianping Xu
- Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College HospitalPeking Union Medical College, Chinese Academy of Medical SciencesBeijingChina
| | - Hongwei Ling
- Department of EndocrinologyThe Affiliated Hospital of Xuzhou Medical UniversityXuzhouChina
| | - Jianlin Geng
- Department of EndocrinologyHarrison International Peace HospitalHengshuiChina
| | - Investigators
- Details of the rest investigators can be found in the supporting informationlist of investigators
| | - Yanli Huang
- CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd.ShijiazhuangChina
| | - Ying Xie
- CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd.ShijiazhuangChina
| | - Huiping Zheng
- CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd.ShijiazhuangChina
| | - Huikun Niu
- CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd.ShijiazhuangChina
| | - Tianhao Zhang
- CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd.ShijiazhuangChina
| | - Jing Yuan
- CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd.ShijiazhuangChina
| | - Xinhua Xiao
- Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College HospitalPeking Union Medical College, Chinese Academy of Medical SciencesBeijingChina
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Idrees T, Castro-Revoredo IA, Migdal AL, Moreno EM, Umpierrez GE. Update on the management of diabetes in long-term care facilities. BMJ Open Diabetes Res Care 2022; 10:10/4/e002705. [PMID: 35858714 PMCID: PMC9305812 DOI: 10.1136/bmjdrc-2021-002705] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Accepted: 05/29/2022] [Indexed: 11/10/2022] Open
Abstract
The number of patients with diabetes is increasing among older adults in the USA, and it is expected to reach 26.7 million by 2050. In parallel, the percentage of older patients with diabetes in long-term care facilities (LTCFs) will also rise. Currently, the majority of LTCF residents are older adults and one-third of them have diabetes. Management of diabetes in LTCF is challenging due to multiple comorbidities and altered nutrition. Few randomized clinical trials have been conducted to determine optimal treatment for diabetes management in older adults in LTCF. The geriatric populations are at risk of hypoglycemia since the majority are treated with insulin and have different levels of functionality and nutritional needs. Effective approaches to avoid hypoglycemia should be implemented in these settings to improve outcome and reduce the economic burden. Newer medication classes might carry less risk of developing hypoglycemia along with the appropriate use of technology, such as the use of continuous glucose monitoring. Practical clinical guidelines for diabetes management including recommendations for prevention and treatment of hypoglycemia are needed to appropriately implement resources in the transition of care plans in this vulnerable population.
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Affiliation(s)
- Thaer Idrees
- Department of Medicine, Division of Endocrinology, Emory University, Atlanta, Georgia, USA
| | - Iris A Castro-Revoredo
- Department of Medicine, Division of Endocrinology, Emory University, Atlanta, Georgia, USA
| | - Alexandra L Migdal
- Department of Medicine, Division of Endocrinology, Emory University, Atlanta, Georgia, USA
| | - Emmelin Marie Moreno
- Department of Medicine, Division of Endocrinology, Emory University, Atlanta, Georgia, USA
| | - Guillermo E Umpierrez
- Department of Medicine, Division of Endocrinology, Emory University, Atlanta, Georgia, USA
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22
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He L, Wang J, Ping F, Yang N, Huang J, Li W, Xu L, Zhang H, Li Y. Dipeptidyl peptidase-4 inhibitors and gallbladder or biliary disease in type 2 diabetes: systematic review and pairwise and network meta-analysis of randomised controlled trials. BMJ 2022; 377:e068882. [PMID: 35764326 PMCID: PMC9237836 DOI: 10.1136/bmj-2021-068882] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To examine the association between dipeptidyl peptidase-4 inhibitors and gallbladder or biliary diseases. DESIGN Systematic review and pairwise and network meta-analysis. DATA SOURCES PubMed, EMBASE, Web of Science, and CENTRAL from inception until 31 July 2021. ELIGIBILITY CRITERIA Randomised controlled trials of adult patients with type 2 diabetes who received dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors compared with placebo or other antidiabetes drugs. MAIN OUTCOME MEASURES Composite of gallbladder or biliary diseases, cholecystitis, cholelithiasis, and biliary diseases. DATA EXTRACTION AND DATA SYNTHESIS Two reviewers independently extracted the data and assessed the quality of the studies. The quality of the evidence for each outcome was assessed using the Grading of Recommendations, Assessment, Development and Evaluations framework (GRADE) approach. The meta-analysis used pooled odds ratios and 95% confidence intervals. RESULTS A total of 82 randomised controlled trials with 104 833 participants were included in the pairwise meta-analysis. Compared with placebo or non-incretin drugs, dipeptidyl peptidase-4 inhibitors were significantly associated with an increased risk of the composite of gallbladder or biliary diseases (odds ratio 1.22 (95%confidence interval 1.04 to 1.43); risk difference 11 (2 to 21) more events per 10 000 person years) and cholecystitis (odds ratio 1.43 (1.14 to 1.79); risk difference 15 (5 to 27) more events per 10 000 person years) but not with the risk of cholelithiasis and biliary diseases. The associations tended to be observed in patients with a longer duration of dipeptidyl peptidase-4 inhibitor treatment. In the network meta-analysis of 184 trials, dipeptidyl peptidase-4 inhibitors increased the risk of the composite of gallbladder or biliary diseases and cholecystitis compared with sodium-glucose cotransporter-2 inhibitors but not compared with glucagon-like peptide-1 receptor agonists. CONCLUSIONS Dipeptidyl peptidase-4 inhibitors increased the risk of cholecystitis in randomised controlled trials, especially with a longer treatment duration, which requires more attention from physicians in clinical practice. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42021271647.
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Affiliation(s)
- Liyun He
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jialu Wang
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fan Ping
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Na Yang
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jingyue Huang
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wei Li
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lingling Xu
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Huabing Zhang
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yuxiu Li
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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23
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Turan B, Durak A, Olgar Y, Tuncay E. Comparisons of pleiotropic effects of SGLT2 inhibition and GLP-1 agonism on cardiac glucose intolerance in heart dysfunction. Mol Cell Biochem 2022; 477:2609-2625. [DOI: 10.1007/s11010-022-04474-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 05/04/2022] [Indexed: 11/29/2022]
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24
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Dar S, Siddiqi AK, Alabduladhem TO, Rashid AM, Sarfraz S, Maniya T, Menezes RG, Almas T. Effects of novel glucose-lowering drugs on the lipid parameters: A systematic review and meta-analysis. Ann Med Surg (Lond) 2022; 77:103633. [PMID: 35637990 PMCID: PMC9142616 DOI: 10.1016/j.amsu.2022.103633] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 04/12/2022] [Accepted: 04/12/2022] [Indexed: 01/10/2023] Open
Affiliation(s)
- Sophia Dar
- Hackensack University Medical Center, Hackensack, NJ, United States
| | | | | | | | - Saba Sarfraz
- Department of Medicine, Islamabad Medical and Dental College, Islamabad, Pakistan
| | - Talha Maniya
- Department of Medicine, Ziauddin Medical University, Karachi, Pakistan
| | - Ritesh G. Menezes
- College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Talal Almas
- Department of Medicine, Royal College of Surgeons in Ireland, Ireland
- Corresponding author.
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25
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Wu LD, Zhou N, Sun JY, Yu H, Wang RX. Effects of sitagliptin on serum lipid levels in patients with type 2 diabetes: a systematic review and meta-analysis. J Cardiovasc Med (Hagerstown) 2022; 23:308-317. [PMID: 35486682 DOI: 10.2459/jcm.0000000000001270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
AIM Lipid abnormalities often occur in patients with diabetes mellitus and the coexistence of diabetes mellitus and dyslipidaemia will increase the risk of cardiovascular diseases. However, the specific effects of sitagliptin on lipid control remain elusive in diabetic patients. The aim of this meta-analysis is to investigate the effects of sitagliptin alone or with other antidiabetic agents on serum lipid control. METHODS PubMed, Cochrane Library, Embase and the ClinicalTrials.gov website were systematically searched from 2006 (the first year that sitagliptin entered market) to 16 January 2021. Eligible studies were randomized clinical trials (RCTs) of sitagliptin including outcomes of serum total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C) or low-density lipoprotein cholesterol (LDL-C). RESULTS A total of 14 RCTs with 2654 patients were identified. Treatment with sitagliptin alone or in combination with other antidiabetic agents significantly reduced serum TC [mean difference (MD) = -5.52 95% confidence interval (95% CI), -7.88 to -3.15; P < 0.00001] and LDL-C (MD = -0.07; 95% CI, -0.14 to 0.00; P < 0.00001) in patients with type 2 diabetes. No statistical significances were found in serum triglycerides (MD = 1.53; 95% CI, -8.22 to 11.28; P = 0.76) or HDL-C (MD = 0.65; 95% CI, -1.59 to 0.29; P = 0.18). Subgroup analyses suggest that sitagliptin can significantly decrease serum LDL-C, TC and triglyceride levels compared with placebo alone, and no statistical significance was found in comparison with the serum HDLC levels. CONCLUSION Sitagliptin alone or in combination with other antidiabetic agents significantly reduces serum TC and LDL-C in patients with type 2 diabetes mellitus, while no significant difference was observed in serum triglycerides or HDL-C.
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Affiliation(s)
- Li-Da Wu
- Department of Cardiology, Wuxi People's Hospital Affiliated to Nanjing Medical University
| | - Nan Zhou
- Department of Nursing, Huadong Sanatorium, Wuxi
| | - Jin-Yu Sun
- Department of Cardiology, Wuxi People's Hospital Affiliated to Nanjing Medical University
| | - Hao Yu
- Department of Orthopedics, Tianjin Medical University General Hospital Affiliated to Tianjin Medical University, Tianjin, China
| | - Ru-Xing Wang
- Department of Cardiology, Wuxi People's Hospital Affiliated to Nanjing Medical University
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26
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Hasan SS, Aslam Q, Islam I, Kow CS, Babar ZUD. Metformin-based single pill drug combinations for type 2 diabetes in primary care England: A time trend analysis. Prim Care Diabetes 2022; 16:271-278. [PMID: 35115253 DOI: 10.1016/j.pcd.2022.01.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 01/17/2022] [Accepted: 01/23/2022] [Indexed: 11/17/2022]
Abstract
AIMS There has been an increase in prescribing and costs of oral hypoglycaemic agents in England and other countries. This study aims to investigate the trends in prescriptions, costs, and adverse events of metformin and metformin-based single pill drug combinations from 2015 to 2020 and explore why changes in use or cost are occurring. METHODS Prescriptions and costs data from Prescription Cost Analysis database and Interactive Drug Analysis Profiles presenting all suspected ADRs reported for each drug were examined. Pharmacy level prices were also obtained. Linear regression analysis was used to investigate the trends in prescribing and costs. RESULTS Prescribing and costs of metformin-based single pill drug combinations (as a percent mean change per year) saw an increase of 8.78% (95% Cl: 7.45%, 10.11%, p = 0.001) and 5.17% (95% Cl: 2.13%, 8.22%, p = 0.009) on average each year, respectively. Metformin was the most prescribed monotherapy drug between 2015 and 2020. The cost of prescribing metformin (as a proportion of total oral hypoglycaemic agents) has been reduced from 30% in 2015 to 17% in 2020. Metformin-dipeptidyl peptidase-4 inhibitor (e.g., metformin-sitagliptin) combination was the most popular metformin-based single pill drug combination. The number of adverse drug reactions per million items dispensed shows that metformin has the lowest adverse drug reactions per million items compared to other oral hypoglycaemic drugs. CONCLUSIONS Overall, an increase in prescription items can be seen for metformin-based single pill drug combinations along with an increase in their costs in primary care in England between 2015 and 2020. There was a declining trend for the number of ADRs reported per million prescription items dispensed for metformin-containing single pill combinations, even though their prescription rate increased.
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Affiliation(s)
- Syed Shahzad Hasan
- Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, United Kingdom.
| | - Qasim Aslam
- Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, United Kingdom
| | - Imarah Islam
- Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, United Kingdom
| | - Chia Siang Kow
- School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia
| | - Zaheer Ud Din Babar
- Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, United Kingdom
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Lasalvia P, Gil-Rojas Y, García Á. Cost-effectiveness of dapagliflozin compared to DPP-4 inhibitors as combination therapy with metformin in the treatment of type 2 diabetes mellitus without established cardiovascular disease in Colombia. Expert Rev Pharmacoecon Outcomes Res 2022; 22:955-964. [PMID: 35259045 DOI: 10.1080/14737167.2022.2044310] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION SGLT2 inhibitors or DPP-4 inhibitors are among the preferred options in patients with type 2 diabetes mellitus (T2DM) without established cardiovascular disease. OBJECTIVE To evaluate the incremental cost-effectiveness of dapagliflozin versus DPP-4 inhibitors as a complement to metformin in the treatment ofT2D, from the perspective of the Colombian health system. METHODS The Cardiff model was used to estimate the incremental cost-effectiveness ratio (ICER) of dapagliflozin plus metformin compared to DPP-4 inhibitors plus metformin in adults with T2DM who did not respond adequately to metformin monotherapy. We estimated the incidence of micro- and macrovascular complications from risk equations incorporating the effect of treatment. The time horizon for analysis was 5 years and a discount rate of 5% was applied, for both costs and outcomes. The costs were expressed in 2020 USD (1 USD = $3,693.36 COP). RESULTS Dapagliflozin in association with metformin resulted in a higher number of quality-adjusted life years (QALYs) compared to the intervention. The ICER was US$1,964.80 per QALY gained. CONCLUSION From the point of view of Colombian healthcare system, the combination of dapagliflozin with metformin is a cost-effective option compared to DPP-4 + metformin inhibitors in the treatment of T2D without established cardiovascular disease.
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Affiliation(s)
| | | | - Ángel García
- Cardiology Unit, San Ignacio University Hospital. Pontificia Universidad Javeriana, Bogotá, Colombia
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Jalaludin MY, Deeb A, Zeitler P, Garcia R, Newfield RS, Samoilova Y, Rosario CA, Shehadeh N, Saha CK, Zhang Y, Zilli M, Scherer LW, Lam RLH, Golm GT, Engel SS, Kaufman KD, Shankar RR. Efficacy and safety of the addition of sitagliptin to treatment of youth with type 2 diabetes and inadequate glycemic control on metformin without or with insulin. Pediatr Diabetes 2022; 23:183-193. [PMID: 34779103 DOI: 10.1111/pedi.13282] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 10/13/2021] [Indexed: 11/28/2022] Open
Abstract
OBJECTIVE To assess the efficacy and safety of sitagliptin in youth with type 2 diabetes (T2D) inadequately controlled with metformin ± insulin. STUDY DESIGN Data were pooled from two 54-week, double-blind, randomized, placebo-controlled studies of sitagliptin 100 mg daily or placebo added onto treatment of 10- to 17-year-old youth with T2D and inadequate glycemic control on metformin ± insulin. Participants (N = 220 randomized and treated) had HbA1c 6.5%-10% (7.0%-10% if on insulin), were overweight/obese at screening or diagnosis and negative for pancreatic autoantibodies. The primary endpoint was change from baseline in HbA1c at Week 20. RESULTS Treatment groups were well balanced at baseline (mean HbA1c = 8.0%, BMI = 30.9 kg/m2 , age = 14.4 years [44.5% <15], 65.9% female). The dose of background metformin was >1500 mg/day for 71.8% of participants; 15.0% of participants were on insulin therapy. At Week 20, LS mean changes from baseline (95% CI) in HbA1c for sitagliptin/metformin and placebo/metformin were -0.58% (-0.94, -0.22) and -0.09% (-0.43, 0.26), respectively; difference = -0.49% (-0.90, -0.09), p = 0.018; at Week 54 the LS mean (95% CI) changes were 0.35% (-0.48, 1.19) and 0.73% (-0.08, 1.54), respectively. No meaningful differences between the adverse event profiles of the treatment groups emerged through Week 54. CONCLUSIONS These results do not suggest that addition of sitagliptin to metformin provides durable improvement in glycemic control in youth with T2D. In this study, sitagliptin was generally well tolerated with a safety profile similar to that reported in adults. (ClinicalTrials.gov: NCT01472367, NCT01760447; EudraCT: 2011-002529-23/2014-003583-20, 2012-004035-23).
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Affiliation(s)
| | - Asma Deeb
- Department of Pediatric Endocrinology, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates
| | - Philip Zeitler
- Department of Endocrinology, Children's Hospital Colorado Clinical, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Raymundo Garcia
- Department of Internal Medicine and Clinical Endocrinology, Centro de Estudios Clínicos y Especialidades Medicas (CECEM), Nuevo Leon, Mexico
| | - Ron S Newfield
- Department of Pediatric Endocrinology, Rady Children's Hospital, University of California San Diego, San Diego, California, USA
| | - Yulia Samoilova
- Department of Pediatric Endocrinology and Diabetology, Siberian State Medical University, Tomsk, Russia
| | - Carmen A Rosario
- Department of Pediatric Endocrinology, Hospital General Plaza de la Salud, Santo Domingo, Dominican Republic
| | - Naim Shehadeh
- Department of Pediatrics A and the Pediatric Diabetes Unit, Institute of Diabetes, Endocrinology, and Metabolism, Rambam Medical Center, Haifa, Israel
| | - Chandan K Saha
- Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Yilong Zhang
- Merck Research Laboratories, Merck & Co., Inc, Kenilworth, New Jersey, USA
| | - Martina Zilli
- Merck Research Laboratories, Merck & Co., Inc, Kenilworth, New Jersey, USA
| | - Lynn W Scherer
- Merck Research Laboratories, Merck & Co., Inc, Kenilworth, New Jersey, USA
| | - Raymond L H Lam
- Merck Research Laboratories, Merck & Co., Inc, Kenilworth, New Jersey, USA
| | - Gregory T Golm
- Merck Research Laboratories, Merck & Co., Inc, Kenilworth, New Jersey, USA
| | - Samuel S Engel
- Merck Research Laboratories, Merck & Co., Inc, Kenilworth, New Jersey, USA
| | - Keith D Kaufman
- Merck Research Laboratories, Merck & Co., Inc, Kenilworth, New Jersey, USA
| | - R Ravi Shankar
- Merck Research Laboratories, Merck & Co., Inc, Kenilworth, New Jersey, USA
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Shankar RR, Zeitler P, Deeb A, Jalaludin MY, Garcia R, Newfield RS, Samoilova Y, Rosario CA, Shehadeh N, Saha CK, Zhang Y, Zilli M, Scherer LW, Lam RLH, Golm GT, Engel SS, Kaufman KD. A randomized clinical trial of the efficacy and safety of sitagliptin as initial oral therapy in youth with type 2 diabetes. Pediatr Diabetes 2022; 23:173-182. [PMID: 34779087 DOI: 10.1111/pedi.13279] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 09/20/2021] [Accepted: 09/29/2021] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE To assess the efficacy and safety of DPP-4 inhibition with sitagliptin in youth with type 2 diabetes (T2D). STUDY DESIGN This was a 54-week, double-blind, randomized, controlled clinical trial evaluating the safety and efficacy of DPP-4 inhibition with sitagliptin 100 mg once daily as initial oral therapy in youth with T2D. The 190 participants, aged 10-17 years, had HbA1c 6.5%-10% (7.0%-10% if on insulin). All were negative for pancreatic autoantibodies and overweight/obese at screening or diagnosis. The trial was placebo controlled for the first 20 weeks, after which metformin replaced placebo. The primary efficacy endpoint was change from baseline in HbA1c at Week 20. RESULTS Treatment groups were well balanced at baseline (mean ± SD HbA1c = 7.5% ± 1.0, BMI percentile = 97.1% ± 6.8, age = 14.0 years ± 2.0 [57.4% <15], 60.5% female). At Week 20, least squares mean changes from baseline in HbA1c were -0.01% (sitagliptin) and 0.18% (placebo); between-group difference (95% CI) = -0.19% (-0.68, 0.30), p = 0.448. At Week 54, the changes in HbA1c were 0.45% (sitagliptin) and -0.11 (placebo/metformin). There were no notable between-group differences in the adverse event profiles through Week 54. CONCLUSIONS DPP-4 inhibition with sitagliptin did not provide significant improvement in glycemic control. In this study, sitagliptin was generally well tolerated with a safety profile similar to that reported in adults. (ClinicalTrials.gov: NCT01485614; EudraCT: 2011-002528-42).
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Affiliation(s)
- R Ravi Shankar
- Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA
| | - Philip Zeitler
- Department of Endocrinology, Children's Hospital Colorado Clinical, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Asma Deeb
- Department of Pediatric Endocrinology, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates
| | | | - Raymundo Garcia
- Department of Internal Medicine and Clinical Endocrinology, Centro de Estudios Clínicos y Especialidades Medicas (CECEM), Nuevo Leon, Mexico
| | - Ron S Newfield
- Department of Pediatric Endocrinology, Rady Children's Hospital, University of California San Diego, San Diego, California, USA
| | - Yulia Samoilova
- Department of Pediatric Endocrinology and Diabetology, Siberian State Medical University, Tomsk, Russia
| | - Carmen A Rosario
- Department of Pediatric Endocrinology, Hospital General Plaza de la Salud, Santo Domingo, Dominican Republic
| | - Naim Shehadeh
- Department of Pediatrics A and the Pediatric Diabetes Unit, Institute of Diabetes, Endocrinology, and Metabolism, Rambam Medical Center, Haifa, Israel
| | - Chandan K Saha
- Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Yilong Zhang
- Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA
| | - Martina Zilli
- Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA
| | - Lynn W Scherer
- Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA
| | - Raymond L H Lam
- Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA
| | - Gregory T Golm
- Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA
| | - Samuel S Engel
- Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA
| | - Keith D Kaufman
- Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA
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Comparative Evaluation of BGR-34 and Sitagliptin in Diabetic Subjects-Open Labelled Randomised Parallel Clinical Study. SERBIAN JOURNAL OF EXPERIMENTAL AND CLINICAL RESEARCH 2021. [DOI: 10.2478/sjecr-2021-0057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Abstract
This article is mainly concerned with the simultaneous open model clinical study of the drug named sitagliptin, a potent hyperglycaemic drug against a novel entity of the natural origin BGR- 34 in diabetic subjects. This was a 3-month randomized, parallel, comparative study. One hundred subjects were planned to be included in the study. The patients were randomly divided into two groups and according to the appropriate sample size analysis, both groups consisted of 100 patients, following the inclusion and exclusion criteria. A total of 90 patients (both male and female) of the mean patient age 30-65 years with the type 2 diabetes were enrolled in the phase 4 of this study and then the data were analyzed on the basis of the different test which included HbA1c (glycated haemoglobin), RBS (random blood sugar), FBS (fasting blood sugar) and PPG (postprandial glucose) values. After completion of the data calibration, the results were analyzed and as a result 10-20% decreased values of HBA1C values accompanied with the RBS, FBS and PPG values were seen in the patients undergoing a 12-week course with BGR-34. Based on the results obtained in the present study, it can be concluded that BGR-34 is effective in reducing high blood sugar levels and this reflects that the BGR-34 therapy is more effective drug in the treatment of diabetes suggesting that it is better in efficacy, and reliability with little or no adverse effects.
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Charoo NA, Abdallah DB, Bakheit AA, Haque KU, Hassan HA, Abrahamsson B, Cristofoletti R, Langguth P, Mehta M, Parr A, Polli JE, Shah VP, Tajiri T, Dressman J. Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Sitagliptin Phosphate Monohydrate. J Pharm Sci 2021; 111:2-13. [PMID: 34597625 DOI: 10.1016/j.xphs.2021.09.031] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 09/15/2021] [Accepted: 09/15/2021] [Indexed: 01/21/2023]
Abstract
Sitagliptin is an antihyperglycemic drug used in adults for the treatment of diabetes Type 2. Literature data and in-house experiments were applied in this monograph to assess whether methods based on the Biopharmaceutics Classification System (BCS) could be used to assess the bioequivalence of solid immediate-release (IR) oral dosage forms containing sitagliptin phosphate monohydrate, as an alternative to a pharmacokinetic study in human volunteers. The solubility and permeability characteristics of sitagliptin were reviewed according to the BCS, along with dissolution, therapeutic index, therapeutic applications, pharmacokinetics, pharmacodynamic characteristics, reports of bioequivalence (BE) / bioavailability problems, data on interactions between the drug and excipients and other data germane to the subject. All data reviewed in this monograph unambiguously support classification of sitagliptin as a BCS Class 1 drug. In light of its broad therapeutic index and lack of severe adverse effects, the clinical risks associated with moderately supraoptimal doses were deemed inconsequential, as were the risks associated with moderately suboptimal doses. Taking all evidence into consideration, it was concluded that the BCS-based biowaiver can be implemented for solid IR oral drug products containing sitagliptin phosphate monohydrate, provided (a) the test product is formulated solely with excipients commonly present in solid IR oral drug products approved in ICH or associated countries and used in amounts commonly applied in this type of product, (b) data in support of the BCS-based biowaiver are obtained using the methods recommended by the WHO, FDA, EMA or ICH and (c) the test product and the comparator product (which is the innovator product in this case) meet all in vitro dissolution specifications provided in the WHO, FDA, EMA or ICH guidance.
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Affiliation(s)
- Naseem A Charoo
- Succor Pharma Solutions, Dubai Science Park, Dubai, United Arab Emirates
| | - Daud B Abdallah
- Department of Pharmaceutics, Faculty of Pharmacy, The National Ribat University, Khartoum, Sudan
| | - Ahmed Abdalla Bakheit
- Department of Pharmaceutics, Faculty of Pharmacy, The National Ribat University, Khartoum, Sudan
| | - Kashif Ul Haque
- Succor Pharma Solutions, Dubai Science Park, Dubai, United Arab Emirates
| | - Hassan Ali Hassan
- Department of Pharmaceutics, Faculty of Pharmacy, University of Khartoum, Sudan
| | - Bertil Abrahamsson
- Oral Product Development, Pharmaceutical Technology & Development, Operations AstraZeneca, Gothenburg, Sweden
| | - Rodrigo Cristofoletti
- Brazilian Health Surveillance Agency (ANVISA), Division of Bioequivalence, Brasilia, Brazil
| | - Peter Langguth
- Department of Pharmaceutical Technology and Biopharmaceutics, Johannes Gutenberg University, Mainz, Germany
| | - Mehul Mehta
- United States Food and Drug Administration, Center for Drug Evaluation and Research, Silver Spring, MD, USA
| | - Alan Parr
- Bioceutics LCC, Raleigh-Durham, North Carolina, USA
| | - James E Polli
- Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD, USA
| | - Vinod P Shah
- International Pharmaceutical Federation (FIP), The Hague, the Netherlands
| | - Tomokazu Tajiri
- Astellas Pharma Inc, Analytical Research Laboratories, Yaizu, Japan
| | - Jennifer Dressman
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany.
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Kazi M, Alqahtani A, Ahmad A, Noman OM, Aldughaim MS, Alqahtani AS, Alanazi FK. Development and optimization of sitagliptin and dapagliflozin loaded oral self-nanoemulsifying formulation against type 2 diabetes mellitus. Drug Deliv 2021; 28:100-114. [PMID: 33345632 PMCID: PMC7875557 DOI: 10.1080/10717544.2020.1859001] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Control of hyperglycemia and prevention of glucose reabsorption (glucotoxicity) are important objectives in the management of type 2 diabetes. This study deals with an oral combined dosage form design for two anti-diabetic drugs, sitagliptin and dapagliflozin using self-nanoemulsifying drug delivery systems (SNEDDS). The SNEDDS were developed using naturally obtained bioactive medium-chain/long-chain triglycerides oil, mixed glycerides and nonionic surfactants, and droplet size was measured followed by the test for antioxidant activities. Equilibrium solubility and dynamic dispersion experiments were conducted to achieve the maximum drug loading. The in vitro digestion, in vivo bioavailability, and anti-diabetic effects were studied to compare the representative SNEDDS with marketed product Dapazin®. The representative SNEDDS containing black seed oil showed excellent self-emulsification performance with transparent appearance. Characterization of the SNEDDS showed nanodroplets of around 50–66.57 nm in size (confirmed by TEM analysis), in addition to the high drug loading capacity without causing any precipitation in the gastro-intestinal tract. The SNEDDS provided higher antioxidant activity compared to the pure drugs. The in vivo pharmacokinetic parameters of SNEDDS showed significant increase in Cmax (1.99 ± 0.21 µg mL−1), AUC (17.94 ± 1.25 µg mL−1), and oral absorption (2-fold) of dapagliflozin compared to the commercial product in the rat model. The anti-diabetic studies showed the significant inhibition of glucose level in treated diabetic mice by SNEDDS combined dose compared to the single drug therapy. The combined dose of sitagliptin-dapagliflozin using SNEDDS could be a potential oral pharmaceutical product for the improved treatment of type 2 diabetes mellitus.
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Affiliation(s)
- Mohsin Kazi
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Abdulmohsen Alqahtani
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Ajaz Ahmad
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Omar M Noman
- Medicinal Aromatic, and Poisonous Plants Research Center, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | | | - Ali S Alqahtani
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Fars K Alanazi
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
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Ennis GE, Kohli A, Jonaitis EM, Betthauser TJ, Oh JM, Taylor CE, Chin N, Koscik RL, Christian BT, Asthana S, Johnson SC, Bendlin BB. The relationship of glucose-stimulated insulin secretion to cerebral glucose metabolism and cognition in healthy middle-aged and older adults. Neurobiol Aging 2021; 105:174-185. [PMID: 34091125 PMCID: PMC8338794 DOI: 10.1016/j.neurobiolaging.2021.04.028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Revised: 11/04/2020] [Accepted: 04/27/2021] [Indexed: 01/04/2023]
Abstract
Insulin resistance (IR) has been related to reduced cerebral glucose metabolism in regions identified as hypometabolic in Alzheimer's clinical syndrome. Insulin secretion (IS) has been less studied than IR despite findings that decreased IS is an early indicator of future type 2 diabetes and a potential predictor of Alzheimer's clinical syndrome. We investigated whether higher IR and lower IS would be associated with greater age-related reductions in regional cerebral glucose metabolism and worse cognitive performance. Two-hour oral glucose tolerance testing and 18F-fluorodeoxyglucose positron emission tomography were performed on 1-2 occasions on a sample of healthy middle-aged and older adults from the Wisconsin Alzheimer's Disease Research Center. Neuropsychological tests were completed during Alzheimer's Disease Research Center Clinical Core visits. Pattern of findings suggested that lower (not higher) IS was related to higher regional cerebral glucose metabolism in middle aged but not older adults, and lower (not higher) IS was also related to better immediate recall. In the context of healthy insulin sensitivity, lower IS may be beneficial to brain health.
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Affiliation(s)
- Gilda E Ennis
- Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
| | - Akshay Kohli
- Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Erin M Jonaitis
- Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Tobey J Betthauser
- Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Jennifer M Oh
- Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Chase E Taylor
- Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Nathaniel Chin
- Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Rebecca L Koscik
- Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Bradley T Christian
- Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, WI, USA; Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA
| | - Sanjay Asthana
- Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Geriatric Research Education and Clinical Center, William S. Middleton Hospital Department of Veterans Affairs, Madison, WI, USA
| | - Sterling C Johnson
- Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Geriatric Research Education and Clinical Center, William S. Middleton Hospital Department of Veterans Affairs, Madison, WI, USA
| | - Barbara B Bendlin
- Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Geriatric Research Education and Clinical Center, William S. Middleton Hospital Department of Veterans Affairs, Madison, WI, USA
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Kelly A, Sheikh S, Stefanovski D, Peleckis AJ, Nyirjesy SC, Eiel JN, Sidhaye A, Localio R, Gallop R, De Leon DD, Hadjiliadis D, Rubenstein RC, Rickels MR. Effect of Sitagliptin on Islet Function in Pancreatic Insufficient Cystic Fibrosis With Abnormal Glucose Tolerance. J Clin Endocrinol Metab 2021; 106:2617-2634. [PMID: 34406395 PMCID: PMC8660013 DOI: 10.1210/clinem/dgab365] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Indexed: 01/21/2023]
Abstract
PURPOSE Impaired incretin secretion may contribute to the defective insulin secretion and abnormal glucose tolerance (AGT) that associate with worse clinical outcomes in pancreatic insufficient cystic fibrosis (PI-CF). The study objective was to test the hypothesis that dipeptidyl peptidase-4 (DPP-4) inhibitor-induced increases in intact incretin hormone [glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)] concentrations augment insulin secretion and glucagon suppression and lower postprandial glycemia in PI-CF with AGT. METHODS 26 adults from Children's Hospital of Philadelphia and University of Pennsylvania CF Center with PI-CF and AGT [defined by oral glucose tolerance test glucose (mg/dL): early glucose intolerance (1-h ≥ 155 and 2-h < 140), impaired glucose tolerance (2-h ≥ 140 and < 200 mg/dL), or diabetes (2-h ≥ 200)] were randomized to a 6-month double-blind trial of DPP-4 inhibitor sitagliptin 100 mg daily or matched placebo; 24 completed the trial (n = 12 sitagliptin; n = 12 placebo). Main outcome measures were mixed-meal tolerance test (MMTT) responses for intact GLP-1 and GIP, insulin secretory rates (ISRs), glucagon suppression, and glycemia and glucose-potentiated arginine (GPA) test-derived measures of β- and α-cell function. RESULTS Following 6-months of sitagliptin vs placebo, MMTT intact GLP-1 and GIP responses increased (P < 0.001), ISR dynamics improved (P < 0.05), and glucagon suppression was modestly enhanced (P < 0.05) while GPA test responses for glucagon were lower. No improvements in glucose tolerance or β-cell sensitivity to glucose, including for second-phase insulin response, were found. CONCLUSIONS In glucose intolerant PI-CF, sitagliptin intervention augmented meal-related incretin responses with improved early insulin secretion and glucagon suppression without affecting postprandial glycemia.
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Affiliation(s)
- Andrea Kelly
- Division of Endocrinology and Diabetes, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
- Correspondence: Andrea Kelly, MD, MSCE, Division of Endocrinology and Diabetes, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA.
| | - Saba Sheikh
- Division of Pulmonary Medicine, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphias, PA, USA
| | - Darko Stefanovski
- Department of Biostatistics, University of Pennsylvania School of Veterinary Medicine, Kennett Square, PA, USA
| | - Amy J Peleckis
- Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Sarah C Nyirjesy
- Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Jack N Eiel
- Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Aniket Sidhaye
- Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Russell Localio
- Department of Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
| | - Robert Gallop
- Department of Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
- Department of Mathematics, West Chester University of Pennsylvania, West Chester, PA, USA
| | - Diva D De Leon
- Division of Endocrinology and Diabetes, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
| | - Denis Hadjiliadis
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Ronald C Rubenstein
- Division of Pulmonary Medicine, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphias, PA, USA
- Division of Allergy and Pulmonary Medicine, Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, MO, USA
| | - Michael R Rickels
- Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
- Michael R. Rickels, MD, MS, Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
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Yoshikawa F, Uchino H, Nagashima T, Usui S, Miyagi M, Ando Y, Hirose T. Dipeptidyl peptidase-4 inhibitor improves glycemic variability in multiple daily insulin-treated type 2 diabetes: a prospective randomized-controlled trial. Diabetol Int 2021; 13:124-131. [DOI: 10.1007/s13340-021-00513-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Accepted: 05/12/2021] [Indexed: 10/21/2022]
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Song Y, Ma P, Gao Y, Xiao P, Xu L, Liu H. A Bibliometrics Analysis of Metformin Development From 1980 to 2019. Front Pharmacol 2021; 12:645810. [PMID: 33995056 PMCID: PMC8113770 DOI: 10.3389/fphar.2021.645810] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Accepted: 02/10/2021] [Indexed: 12/13/2022] Open
Abstract
Metformin, the first-line oral blood glucose-lowering agent to manage type 2 diabetes, has gained growing popularity on both clinical application and basic research since early 1980s. A thorough and systematic knowledge map of metformin is pertinent to evaluate the research frontier and determine knowledge gaps. To this end, 20, 526 publications were analyzed by bibliometrics and data visualization to demonstrate the current global research status, potential hotspots, and perspectives on future research directions. In addition, the metformin development along the historical line was illustrated over the last 40 years. In sum, this study provides a comprehensive analysis that delineates the evolution of the historical milestones of metformin development, and we discuss the future research directions based on objective data analysis from a wide spectrum of metformin research areas.
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Affiliation(s)
- Yanjun Song
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Pei Ma
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Yu Gao
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Peigen Xiao
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Lijia Xu
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Haibo Liu
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
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Lillich FF, Imig JD, Proschak E. Multi-Target Approaches in Metabolic Syndrome. Front Pharmacol 2021; 11:554961. [PMID: 33776749 PMCID: PMC7994619 DOI: 10.3389/fphar.2020.554961] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 11/03/2020] [Indexed: 12/13/2022] Open
Abstract
Metabolic syndrome (MetS) is a highly prevalent disease cluster worldwide. It requires polypharmacological treatment of the single conditions including type II diabetes, hypertension, and dyslipidemia, as well as the associated comorbidities. The complex treatment regimens with various drugs lead to drug-drug interactions and inadequate patient adherence, resulting in poor management of the disease. Multi-target approaches aim at reducing the polypharmacology and improving the efficacy. This review summarizes the medicinal chemistry efforts to develop multi-target ligands for MetS. Different combinations of pharmacological targets in context of in vivo efficacy and future perspective for multi-target drugs in MetS are discussed.
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Affiliation(s)
- Felix F. Lillich
- Institute of Pharmaceutical Chemistry, Goethe-University of Frankfurt, Frankfurt, Germany
| | - John D. Imig
- Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, United States
| | - Ewgenij Proschak
- Institute of Pharmaceutical Chemistry, Goethe-University of Frankfurt, Frankfurt, Germany
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Yang W, Cai X, Zhang S, Han X, Ji L. Dipeptidyl peptidase-4 inhibitor treatment and the risk of bullous pemphigoid and skin-related adverse events: A systematic review and meta-analysis of randomized controlled trials. Diabetes Metab Res Rev 2021; 37:e3391. [PMID: 32741073 DOI: 10.1002/dmrr.3391] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Revised: 07/16/2020] [Accepted: 07/17/2020] [Indexed: 12/24/2022]
Abstract
AIMS This meta-analysis aimed to evaluate the risk of developing bullous pemphigoid (BP) and other skin-related adverse events (AEs) in patients with type 2 diabetes (T2DM) undergoing dipeptidyl peptidase-4 inhibitor (DPP-4i) treatment in randomized controlled trials (RCTs). METHODS In this meta-analysis, the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases were searched for RCTs, which involve patients with T2DM reporting skin-related AEs. RCTs that comparatively evaluated the effects of DPP-4i treatment and placebo on patients with T2DM and reported skin-related AEs were included in the analysis. The odds ratio (OR) and 95% confidence interval (CI) were calculated using the Peto's methods. The GRADE approach was used to rate the quality of evidence. RESULTS A total of 46 randomized placebo-controlled trials, including 3 trials with reports of BP (n = 38 011), that reported skin-related AEs were included (n = 59 332). Compared to the placebo group, the risk of developing BP was significantly higher in the DPP-4i treatment group (OR = 7.38, 95% CI 2.00-27.25, I2 = 0%, P = .003; quality rating: very low). Additionally, DPP-4i treatment was associated with an increased overall risk of developing skin-related AEs (OR = 1.22, 95% CI 1.02-1.46, I2 = 32%, P = .03; quality rating: moderate). CONCLUSIONS This meta-analysis suggested that treatment with DPP-4is, including sitagliptin, saxagliptin, and linagliptin, was associated with an increased risk of developing BP. Additionally, the risk of developing skin-related AEs increased when all DPP-4is were combined. Skin lesion, especially BP, should be monitored in patients with diabetes undergoing DPP-4i treatment. Future studies should evaluate the susceptible population and develop strategies for early detection of skin-related AEs.
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Affiliation(s)
- Wenjia Yang
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Xiaoling Cai
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Simin Zhang
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Xueyao Han
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Linong Ji
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
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Ji L, Li L, Ma J, Li X, Li D, Meng B, Lu W, Sun J, Liu Y, Takayanagi G, Wang Y. Efficacy and safety of teneligliptin added to metformin in Chinese patients with type 2 diabetes mellitus inadequately controlled with metformin: A phase 3, randomized, double-blind, placebo-controlled study. ENDOCRINOLOGY DIABETES & METABOLISM 2021; 4:e00222. [PMID: 33855222 PMCID: PMC8029565 DOI: 10.1002/edm2.222] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 12/09/2020] [Accepted: 12/19/2020] [Indexed: 11/11/2022]
Abstract
Introduction We evaluated the efficacy and safety of teneligliptin compared with placebo when added to metformin therapy in Chinese patients with type 2 diabetes inadequately controlled with metformin monotherapy. Methods This multicentre, randomized, double-blind, placebo-controlled, parallel-group study enrolled type 2 diabetes patients with glycosylated haemoglobin (HbA1c) 7.0%-<10.0% and fasting plasma glucose (FPG) <270 mg/dl, receiving a stable metformin dose ≥1000 mg/day. Teneligliptin 20 mg or placebo was administered orally once daily (qd) before breakfast for 24 weeks. The primary efficacy end-point was change in HbA1c from baseline to Week 24. Safety end-points included the incidence of adverse events (AEs). Results The least square mean (LSM) change from baseline (standard error [SE]) was -0.72 (0.07) (95% confidence intervals [CI], -0.87, -0.58) for teneligliptin and -0.01 (0.07) (95% CI, -0.16, 0.13) for placebo. The differences (LSM ± SE) between the placebo and teneligliptin groups in HbA1c and FPG were -0.71% ± 0.11% (p < .0001) and -16.5 ± 4.7 mg/dl (p = .0005), respectively. Teneligliptin yielded significant changes in HbA1c (-0.81%; p < .0001) and FPG (-22.2 mg/dl; p < .0001) at Week 12. At Week 24, more patients achieved HbA1c <7.0% with teneligliptin (41.7%) compared with placebo (16.1%; p < .0001). Treatment-emergent AE incidence was similar with teneligliptin (58.9%) and placebo (68.3%); upper respiratory tract infection, hyperuricaemia and hyperlipidaemia were the most common AEs. Conclusions Teneligliptin 20 mg qd for 24 weeks added to ongoing metformin treatment significantly decreased HbA1c and FPG levels compared with placebo in Chinese type 2 diabetes patients. The combination was safe and tolerable.
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Affiliation(s)
- Linong Ji
- Peking University People's Hospital Beijing China
| | - Ling Li
- Shengjing Hospital of China Medical University Liaoning China
| | - Jianhua Ma
- Nanjing First Hospital Nanjing Jiangsu China
| | | | - Dongmei Li
- Inner Mongolia People's Hospital Inner Mongolia China
| | - Bangzhu Meng
- The Affiliated Hospital of Inner Mongolia University for Nationalities Inner Mongolia China
| | - Weiping Lu
- Huai'an First People's Hospital Nanjing Medical University Nanjing Jiangsu China
| | - Jiao Sun
- Huadong Hospital Affiliated to Fudan University Shanghai China
| | - Yanmei Liu
- Yancheng City No.1 People's Hospital Jiangsu China
| | - Gen Takayanagi
- Mitsubishi Tanabe Pharma Development America, Inc. Jersey City NJ USA
| | - Yi Wang
- Mitsubishi Tanabe Pharma Development (Beijing) Co., Ltd. Beijing China
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Abstract
Since the recognition of angiotensin-converting enzyme inhibitors (ACEIs)-induced cough, drug has been considered as a potential cause of chronic cough. This review presents recent knowledge on drug-induced coughs in patients with chronic cough. The focus is placed on ACEIs, for which there are a multitude of studies documenting their associations with cough. Additional drugs are discussed for which there are reports of cough as a side effect of treatment, and the potential mechanisms of these effects are discussed.
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Affiliation(s)
- J-S Shim
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul,
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Lautsch D, Alsumali A, McLeod E, Kuang Y, He J, Singh R, Nevo A, Arnet U, Uyei J, Rajpathak S. Comparative Efficacy of Dual and Single Initiation of Add-On Oral Antihyperglycemic Agents in Type 2 Diabetes Uncontrolled on Metformin Alone: A Systematic Literature Review and Network Meta-Analysis. Diabetes Ther 2021; 12:389-418. [PMID: 33313996 PMCID: PMC7843850 DOI: 10.1007/s13300-020-00975-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Accepted: 11/19/2020] [Indexed: 02/06/2023] Open
Abstract
INTRODUCTION Current guidelines recommend adding an oral antihyperglycemic agent (AHA) to metformin in patients with type 2 diabetes mellitus (T2DM) uncontrolled on metformin. Recent randomized clinical trials (RCTs) have demonstrated that adding dual AHAs instead of a single AHA provided more effective glycemic control. However, the comparative efficacy of approved single and dual initiation strategies is unknown. Therefore, we conducted a Bayesian network meta-analysis to compare the efficacy of dual and single add-on oral AHAs in patients uncontrolled on metformin. METHODS A systematic literature review of RCTs was conducted following Cochrane and ISPOR guidelines. MEDLINE, Embase, and CENTRAL were searched from inception to November 19, 2019. Approved oral doses of sodium-glucose co-transporter-2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists in single or dual initiation therapies were indirectly compared. Outcomes focused on efficacy and included mean change from baseline in hemoglobin A1c (HbA1c), weight, systolic blood pressure (SBP), diastolic blood pressure, and achieving HbA1c target < 7% at 24-26 weeks. Fixed and random effects models with Markov chain Monte Carlo simulations were used. RESULTS Of 1955 unique records screened, 25 RCTs (14,264 participants) were included. In patients uncontrolled on metformin, dual AHA added to metformin had statistically significant or a trend of greater reduction in HbA1c compared to single AHAs, with ertugliflozin + sitagliptin showing the greatest improvement. Statistically significant reductions in weight and SBP were observed with ertugliflozin + sitagliptin, ertugliflozin, or canagliflozin compared to single initiation DPP-4 inhibitors. CONCLUSION For reduction of HbA1c, weight, and SBP in patients uncontrolled on metformin, add-on dual AHAs showed greater improvement compared to single AHAs. These findings can further inform the treatment of T2DM patients uncontrolled on metformin.
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Affiliation(s)
- Dominik Lautsch
- Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
| | - Adnan Alsumali
- Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA
| | | | | | - Jing He
- IQVIA, Inc., San Francisco, CA, USA
| | | | | | - Urs Arnet
- Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA
| | | | - Swapnil Rajpathak
- Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA
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Das A, Gandhi P, Saboo B, Reddy S, Chawla R, Zargar A, Kovil R, Chawla M, Sharma SK, Gupta S, Makkar BM, Mittal V, Goswami S, Arvind SR, Jaggi S, Bajaj S, Das S. Optimizing the treatment of newly diagnosed type 2 diabetes mellitus with combination of dipeptidyl peptidase-4 inhibitors and metformin: An expert opinion. J Family Med Prim Care 2021; 10:4398-4409. [PMID: 35280631 PMCID: PMC8884309 DOI: 10.4103/jfmpc.jfmpc_2378_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 02/20/2021] [Accepted: 07/09/2021] [Indexed: 11/22/2022] Open
Abstract
The expanding burden of Type 2 Diabetes Mellitus (T2DM) in today's world, with respect to incidence, prevalence, and cost incurred, is an existential risk to society. Various guidelines recommend individualization of treatment. This expert opinion aims to review the recent evidences and reach a consensus on the preferable combination therapy for use in newly diagnosed Indian T2DM patients with HbA1C >7.5%. The core committee included seventeen diabetes specialists. Three statements were developed, discussed, and rated by specialists and recommendations were noted. Specialists were requested to rate the statements using a 9-point Likert's scale with score of 1 being “Strongly Disagree” and 9 being “Strongly Agree”. Statement-specific scores of all the specialists were added and mean score of ≥7.00 was considered to have achieved a consensus. Statements used to meet the consensus were: Statement 1. Majority of newly-diagnosed Indian diabetics have HbA1C >7.5%; Statement 2. Patients with HbA1C >7.5% may be initiated with dual therapy of dipeptidyl peptidase-4 inhibitors (DPP4Is) + Metformin; and Statement 3. In Indian patients with HbA1C >7.5% at diagnosis, DPP4Is + Metformin may be considered as a first-line therapy. Literature review revealed that HbA1C level at the time of diagnosis in majority of Indian T2DM patients is >7.5%. Consensus was reached that dual anti-diabetic therapy should be initiated in patients with HbA1C >7.5%. DPP4Is + Metformin is the preferred cost-effective option and may be considered as a first-line therapy in Indian T2DM patients with HbA1C >7.5% at diagnosis.
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Kalyani A, Kuchya S, Punekar P. A single-center, observational, retrospective cost-effective analysis of treating inadequately controlled type 2 diabetes mellitus by addition of dpp4 inhibitors versus intensified treatment with conventional drugs. J Pharmacol Pharmacother 2021. [DOI: 10.4103/jpp.jpp_22_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Jia S, Wang Z, Han R, Zhang Z, Li Y, Qin X, Zhao M, Xiang R, Yang J. Incretin mimetics and sodium-glucose co-transporter 2 inhibitors as monotherapy or add-on to metformin for treatment of type 2 diabetes: a systematic review and network meta-analysis. Acta Diabetol 2021; 58:5-18. [PMID: 32514989 DOI: 10.1007/s00592-020-01542-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 04/27/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE Although there are many different methods of treating type 2 diabetes (T2D), it is still difficult to draw coincident conclusions concerning the efficacy and safety of different classes of new drugs, and the recommendation level of them has still kept uncertain as second anti-diabetic agents. Therefore, the aim of this study was to summarize evidence on the efficacy and safety of DPP-4is, GLP-1RAs and SGLT-2is as monotherapy or add-on to metformin (Met) for treatment of T2D. MATERIALS AND METHODS We searched PubMed, Embase, Cochrane library and ClinicalTrials.gov for relevant articles in keeping with established methods using terms associated with anti-diabetic agents up to February, 2020, with no start date restriction. Weighted mean difference and risk ratios with 95% confidence intervals were calculated within traditional and network meta-analysis. Primary outcomes were the mean change in hemoglobin A1c (HbA1c), fasting plasma glucose (FPG) change and the frequency of hypoglycemic events from baseline after 12 weeks of treatment. RESULTS In total, 64 eligible studies comprising 37,780 patients and 7 treatment strategies were included. The results of primary outcomes showed that GLP-1RAs were significantly more effective than DPP-4is or SGLT-2is in reducing HbA1c when add-on to Met. For FPG, both GLP-1RAs and SGLT-2is significantly reduced FPG compared with DPP-4is whether add-on to Met or not. For hypoglycemia, monotherapy has a lower risk than combination therapy except for SGLT-2is. Ranking probability analysis indicated that GLP-1RAs and SGLT-2is, respectively, reduced HbA1c and FPG most when add-on to Met. Meanwhile, GLP-1RAs took the lowest risk to induce the hypoglycemia, whereas GLP-1RAs plus Met the highest. CONCLUSIONS Both GLP-1RAs and SGLT-2is have their own advantages in efficacy and safety. Monotherapy is beneficial for reducing the risk of hypoglycemia. The recommendation should be a patient-centered approach when selecting treatment choices.
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Affiliation(s)
- Shubing Jia
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China
| | - Zhiying Wang
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China
| | - Ruobing Han
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China
| | - Zinv Zhang
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China
| | - Yuping Li
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China
| | - Xiaotong Qin
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China
| | - Mingyi Zhao
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China
| | - Rongwu Xiang
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
| | - Jingyu Yang
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
- Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, China.
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Lin C, Cai X, Yang W, Lv F, Nie L, Ji L. Age, sex, disease severity, and disease duration difference in placebo response: implications from a meta-analysis of diabetes mellitus. BMC Med 2020; 18:322. [PMID: 33190640 PMCID: PMC7667845 DOI: 10.1186/s12916-020-01787-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 09/17/2020] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND The placebo response in patients with diabetes mellitus is very common. A systematic evaluation needs to be updated with the current evidence about the placebo response in diabetes mellitus and the associated factors in clinical trials of anti-diabetic medicine. METHODS Literature research was conducted in Medline, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for studies published between the date of inception and June 2019. Randomized placebo-controlled trials conducted in type 1and type 2 diabetes mellitus (T1DM/T2DM) were included. Random-effects model and meta-regression analysis were accordingly used. This meta-analysis was registered in PROSPERO as CRD42014009373. RESULTS Significantly weight elevation (effect size (ES) = 0.33 kg, 95% CI, 0.03 to 0.61 kg) was observed in patients with placebo treatments in T1DM subgroup while significantly HbA1c reduction (ES = - 0.12%, 95% CI, - 0.16 to - 0.07%) and weight reduction (ES = - 0.40 kg, 95% CI, - 0.50 to - 0.29 kg) were observed in patients with placebo treatments in T2DM subgroup. Greater HbA1c reduction was observed in patients with injectable placebo treatments (ES = - 0.22%, 95% CI, - 0.32 to - 0.11%) versus oral types (ES = - 0.09%, 95% CI, - 0.14 to - 0.04%) in T2DM (P = 0.03). Older age (β = - 0.01, 95% CI, - 0.02 to - 0.01, P < 0.01) and longer diabetes duration (β = - 0.02, 95% CI, - 0.03 to - 0.21 × 10-2, P = 0.03) was significantly associated with more HbA1c reduction by placebo in T1DM. However, younger age (β = 0.02, 95% CI, 0.01 to 0.03, P = 0.01), lower male percentage (β = 0.01, 95% CI, 0.22 × 10-2, 0.01, P < 0.01), higher baseline BMI (β = - 0.02, 95% CI, - 0.04 to - 0.26 × 10-2, P = 0.02), and higher baseline HbA1c (β = - 0.09, 95% CI, - 0.16 to - 0.01, P = 0.02) were significantly associated with more HbA1c reduction by placebo in T2DM. Shorter diabetes duration (β = 0.06, 95% CI, 0.06 to 0.10, P < 0.01) was significantly associated with more weight reduction by placebo in T2DM. However, the associations between baseline BMI, baseline HbA1c, and placebo response were insignificant after the adjusted analyses. CONCLUSION The placebo response in diabetes mellitus was systematically outlined. Age, sex, disease severity (indirectly reflected by baseline BMI and baseline HbA1c), and disease duration were associated with placebo response in diabetes mellitus. The association between baseline BMI, baseline HbA1c, and placebo response may be the result of regression to the mean.
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Affiliation(s)
- Chu Lin
- Department of Endocrinology and Metabolism, Peking University People's Hospital, No.11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
| | - Xiaoling Cai
- Department of Endocrinology and Metabolism, Peking University People's Hospital, No.11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
| | - Wenjia Yang
- Department of Endocrinology and Metabolism, Peking University People's Hospital, No.11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
| | - Fang Lv
- Department of Endocrinology and Metabolism, Peking University People's Hospital, No.11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
| | - Lin Nie
- Department of Endocrinology and Metabolism, Beijing Airport Hospital, Beijing, China
| | - Linong Ji
- Department of Endocrinology and Metabolism, Peking University People's Hospital, No.11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
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Ram H, Jaipal N, Kumar P, Deka P, Kumar S, Kashyap P, Kumar S, Singh BP, Alqarawi AA, Hashem A, Tabassum B, Abd Allah EF. Dual Inhibition of DPP-4 and Cholinesterase Enzymes by the Phytoconstituents of the Ethanolic Extract of Prosopis cineraria Pods: Therapeutic Implications for the Treatment of Diabetes-associated Neurological Impairments. Curr Alzheimer Res 2020; 16:1230-1244. [PMID: 31797759 DOI: 10.2174/1567205016666191203161509] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 11/17/2019] [Accepted: 12/02/2019] [Indexed: 01/11/2023]
Abstract
BACKGROUND Insulin resistance causes decreased uptake of glucose which promotes the susceptibility of type 2 associated neurological impairments. METHODS The study was aimed to evaluate the inhibition potential of the ethanolic extract of Prosopis cineraria (EPC) pods against DPP-4 and cholinesterase enzymes by in-vitro, in-vivo and in-silico assessments. The present study consists of in vivo studies on a diabetes-induced rat model by HOMA (Homeostasis model assessment) and related parameters, in vitro studies through the DPP-4 enzyme assay and cholinesterase assays using Ellman's reaction. The in-silico studies were conducted by the molecular docking of Cinerin C with targeted enzymes. The phytochemical characterization of the extract was demonstrated through LCMS studies. The antioxidant studies on the extract were performed by FRAP and TEAC assays. RESULTS The extract showed 64.8% maximum inhibition of DPP-4, 34.91% inhibition of AChE and 74.35% inhibition of BuChE. The antioxidant capacity of the extract was observed to be 847.81±16.25μM Fe2+ equivalent in the FRAP assay and 0.40 ± 0.08 mmol/l of Trolox equivalent in the TEAC assay. The in vivo study showed competent glycaemic control against significant HOMA IR (1.5), HOMA % β (26.5) and HOMA % S (68.8) as well as pancreatic cell mass proliferation. The insilico analysis also revealed positive interactions of Cinerin C with targeted enzymes (DPP4 and cholinesterase). CONCLUSION It can be concluded that the phytoconstituents of Prosopis cineraria pod extract can be significantly considered in neuropharmacology to resolve insulin resistance-induced neurological complications as it showed inhibition against DPP-4, AChE and BuChE target enzymes.
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Affiliation(s)
- Heera Ram
- Department of Zoology, Jai Narain Vyas University, Jodhpur (Rajasthan)-342001, India
| | - Noopur Jaipal
- Department of Zoology, Jai Narain Vyas University, Jodhpur (Rajasthan)-342001, India
| | - Pramod Kumar
- Department of Zoology, Jai Narain Vyas University, Jodhpur (Rajasthan)-342001, India
| | - Purbajyoti Deka
- Department of Biotechnology, Mizoram University, Aizawl, Mizoram, India
| | - Shivani Kumar
- University School of Biotechnology, GGS Indraprastha University, Dwarka, Sector 16C, New Delhi 110075, India
| | - Priya Kashyap
- University School of Biotechnology, GGS Indraprastha University, Dwarka, Sector 16C, New Delhi 110075, India
| | - Suresh Kumar
- University School of Biotechnology, GGS Indraprastha University, Dwarka, Sector 16C, New Delhi 110075, India
| | - Bhim P Singh
- Department of Biotechnology, Mizoram University, Aizawl, Mizoram, India
| | - Abdulaziz A Alqarawi
- Plant Production Department, College of Food and Agricultural Sciences, King Saud University, P.O. Box. 2460, Riyadh 11451, Saudi Arabia
| | - Abeer Hashem
- Botany and Microbiology Department, College of Science, King Saud University, P.O. Box. 2460, Riyadh 11451, Saudi Arabia.,Mycology and Plant Disease Survey Department, Plant Pathology Research Institute, ARC, Giza 12511, Egypt
| | - Baby Tabassum
- Toxicology Laboratory, Department of Zoology, Govt. Raza P.G. College Rampur, 244901, U.P, India
| | - Elsayed Fathi Abd Allah
- Plant Production Department, College of Food and Agricultural Sciences, King Saud University, P.O. Box. 2460, Riyadh 11451, Saudi Arabia
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Campbell SA, Light PE, Simpson SH. Costarting sitagliptin with metformin is associated with a lower likelihood of disease progression in newly treated people with type 2 diabetes: a cohort study. Diabet Med 2020; 37:1715-1722. [PMID: 31618475 DOI: 10.1111/dme.14154] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/14/2019] [Indexed: 01/17/2023]
Abstract
AIM To examine whether early addition of sitagliptin to metformin is associated with a delay in type 2 diabetes progression. METHODS Administrative health records from Alberta, Canada, for the period April 2008 to March 2015, were used to conduct a retrospective cohort study in new metformin users. People who started sitagliptin on the same day they initiated metformin therapy were compared with those who added sitagliptin later. Insulin initiation served as a surrogate marker for diabetes progression, and multivariable logistic regression models were used to evaluate the association with sitagliptin addition (costart vs later use). A mixed-effects linear regression model was used to examine the effect of timing of sitagliptin addition on HbA1c change over 1 year. RESULTS The mean (sd) age of the 8764 people who used sitagliptin was 52.1 (11.1) years, 5665 (64.6%) were men, and 1153 (13.2%) started sitagliptin on the same day as metformin. Insulin was added to the therapy of 173 (15.0%) costarters and 1453 (19.1%) later sitagliptin users. The adjusted odds ratio for adding insulin was 0.76 (95% CI 0.64 to 0.90) in favour of costarting sitagliptin. HbA1c levels decreased in both groups 1 year after starting sitagliptin, with costarters having a significantly greater reduction [absolute between-group difference of 0.5% (95% CI 0.3 to 0.7)] compared with later sitagliptin users. CONCLUSION Costarting drug therapy with sitagliptin and metformin was associated with a lower likelihood of disease progression in people with type 2 diabetes compared with adding sitagliptin later.
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Affiliation(s)
- S A Campbell
- Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
- Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - P E Light
- Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
- Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - S H Simpson
- Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
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Fang H, Xu F, Du J, Liang L, Li W, Shen L, Wang X, Xu C, Bian F, Mu Y. Impact of baseline characteristics on glycemic effects of add-on saxagliptin or acarbose to metformin therapy: Subgroup analysis of the SMART study in Chinese patients with type 2 diabetes mellitus. J Diabetes Investig 2020; 11:896-905. [PMID: 32020731 PMCID: PMC7378448 DOI: 10.1111/jdi.13224] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 01/22/2020] [Accepted: 01/30/2020] [Indexed: 11/27/2022] Open
Abstract
AIMS/INTRODUCTION This secondary analysis of the 24-week SMART study examined the efficacy of add-on saxagliptin or acarbose to metformin across different patient subgroups with type 2 diabetes mellitus, based on baseline characteristics. MATERIALS AND METHODS Randomized patients (n = 481) were classified into subgroups based on their baseline age (<65, ≥65 years), body mass index (BMI; <24, 24-<28, ≥28 kg/m2 ), glycated hemoglobin (HbA1c; <8%, 8-<9%, 9-<10%, ≥10%) and renal function (creatinine clearance 50-<80, ≥80 mL/min). Treatment effects on primary outcome (HbA1c) and key secondary outcomes of fasting plasma glucose (FPG), 2-h postprandial glucose and homeostatic model assessment of β-cell function were assessed across patient subgroups. RESULTS For saxagliptin, reductions in HbA1c from baseline to week 24 were consistent across different subgroups regardless of baseline age, body mass index, HbA1c and renal function (range -0.66 to -1.16%). Saxagliptin was associated with consistent reductions in FPG (-0.60 to -1.33 mmol/L) and 2-h postprandial glucose (-0.48 to -1.95 mmol/L) across the majority of subgroups studied. The efficacy of acarbose on FPG attenuated progressively with increasing baseline HbA1c (+0.86 to -1.43 mmol/L); an increase from baseline FPG was observed in patients with HbA1c >9%. The effect of acarbose on postprandial glucose was also variable (+0.23 to -3.38 mmol/L). CONCLUSIONS As add-on to metformin, both saxagliptin and acarbose reduced HbA1c regardless of baseline HbA1c, age, body mass index and renal function; however, only saxagliptin was effective at a stable glycemic control (FPG and PPG). The efficacy of acarbose on FPG and PPG was significantly attenuated in patients with higher baseline HbA1c (≥8%).
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Affiliation(s)
- Hui Fang
- Department of EndocrinologyTangshan Gongren HospitalTangshanChina
| | - Fengmei Xu
- Department of EndocrinologyHebi Coal (Group) Co. Ltd, General HospitalHebiChina
| | - Jin Du
- Department of EndocrinologyChinese People’s Liberation Army General HospitalBeijingChina
| | - Li Liang
- Department of EndocrinologyPeople’s Hospital of Liaoning ProvinceShenyangChina
| | - Wei Li
- Department of EndocrinologyAffiliated Hospital of Xuzhou Medical UniversityXuzhouChina
| | - Liya Shen
- Department of GeriatricsWuhan 6th HospitalWuhanChina
| | - Xueying Wang
- Department of EndocrinologyJinzhou Central HospitalJinzhouChina
| | - Chun Xu
- Department of EndocrinologyChinese People’s Armed Police Force General HospitalBeijingChina
| | - Fang Bian
- Department of EndocrinologyCangzhou People’s HospitalCangzhouChina
| | - Yiming Mu
- Department of EndocrinologyChinese People’s Liberation Army General HospitalBeijingChina
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Zhang Z, Yan X, Wu C, Pei X, Li X, Wang X, Niu X, Jiang H, Zeng X, Zhou Z. Adding vitamin D3 to the dipeptidyl peptidase-4 inhibitor saxagliptin has the potential to protect β-cell function in LADA patients: A 1-year pilot study. Diabetes Metab Res Rev 2020; 36:e3298. [PMID: 32043288 DOI: 10.1002/dmrr.3298] [Citation(s) in RCA: 15] [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: 03/18/2019] [Revised: 12/18/2019] [Accepted: 02/03/2020] [Indexed: 12/15/2022]
Abstract
AIMS This trial was conducted to explore the protective effect on β-cell function of adding vitamin D3 to DPP-4 inhibitors to treat patients with latent autoimmune diabetes in adults (LADA). METHODS 60 LADA patients were randomized to group A (n = 21) - conventional therapy with metformin (1-1.7 g/day) and/or insulin treatment; group B (n = 20) - saxagliptin (5 mg/day) plus conventional therapy; and group C (n = 19) - vitamin D3 (2000 IU/day) plus saxagliptin and conventional therapy for 12 months. Fasting and 2-hour postprandial blood samples were collected to measure blood glucose, glycosylated hemoglobin and C-peptide levels at baseline and after 3, 6 and 12 months of treatment. RESULTS During the 12 months of follow-up, the levels of fasting C-peptide (FCP), 2-hour postprandial C-peptide (PCP) and the C-peptide index (CPI, serum C-peptide-to-plasma glucose level ratio) were maintained in group C. In contrast to those in group A and group B, FCP levels decreased significantly in group B, and CPI levels declined significantly in group A during the 1-year treatment (P < .05). Additionally, the levels of GADA titers in group C significantly decreased compared with those at baseline (P < .05), but no significant differences in GADA titers levels were detected in group A and group B. No significant differences were found among the three groups in the levels of FCP, PCP, the CPI or GADA titers. CONCLUSIONS The data suggested that adding 2000 IU/day vitamin D3 to saxagliptin might preserve β-cell function in patients with LADA.
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Affiliation(s)
- Ziwei Zhang
- Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, China
- Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, China
| | - Xiang Yan
- Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, China
- Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, China
| | - Chao Wu
- Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, China
- Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, China
| | - Xieyi Pei
- Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, China
- Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, China
| | - Xia Li
- Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, China
- Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, China
| | - Xiangbing Wang
- Division of Endocrinology, Metabolism, and Nutrition, Rutgers University-Robert Wood Johnson Medical School, New Brunswick, New Jersey
| | - Xiaohong Niu
- Department of Endocrinology, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, China
| | - Hongwei Jiang
- Department of Endocrinology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Xiaomin Zeng
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China
| | - Zhiguang Zhou
- Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, China
- Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, China
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Royer C, Guay‐Bégin A, Chanseau C, Chevallier P, Bordenave L, Laroche G, Durrieu M. Bioactive micropatterning of biomaterials for induction of endothelial progenitor cell differentiation: Acceleration of in situ endothelialization. J Biomed Mater Res A 2020; 108:1479-1492. [DOI: 10.1002/jbm.a.36918] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Revised: 02/24/2020] [Accepted: 03/09/2020] [Indexed: 01/07/2023]
Affiliation(s)
- Caroline Royer
- Univ. BordeauxChimie et Biologie des Membranes et Nano‐Objets (UMR5248 CBMN) Pessac France
- CNRSCBMN UMR5248 Pessac France
- Bordeaux INPCBMN UMR5248 Pessac France
- Laboratoire d'Ingénierie de SurfaceCentre de recherche du CHU de Québec—Université Laval, Hôpital Saint‐François d'Assise Québec Quebec Canada
- Département de génie des minesde la métallurgie et des matériaux, Centre de Recherche sur les Matériaux Avancés Québec Quebec Canada
| | - Andrée‐Anne Guay‐Bégin
- Laboratoire d'Ingénierie de SurfaceCentre de recherche du CHU de Québec—Université Laval, Hôpital Saint‐François d'Assise Québec Quebec Canada
| | | | - Pascale Chevallier
- Laboratoire d'Ingénierie de SurfaceCentre de recherche du CHU de Québec—Université Laval, Hôpital Saint‐François d'Assise Québec Quebec Canada
- Département de génie des minesde la métallurgie et des matériaux, Centre de Recherche sur les Matériaux Avancés Québec Quebec Canada
| | | | - Gaétan Laroche
- Laboratoire d'Ingénierie de SurfaceCentre de recherche du CHU de Québec—Université Laval, Hôpital Saint‐François d'Assise Québec Quebec Canada
- Département de génie des minesde la métallurgie et des matériaux, Centre de Recherche sur les Matériaux Avancés Québec Quebec Canada
| | - Marie‐Christine Durrieu
- Univ. BordeauxChimie et Biologie des Membranes et Nano‐Objets (UMR5248 CBMN) Pessac France
- CNRSCBMN UMR5248 Pessac France
- Bordeaux INPCBMN UMR5248 Pessac France
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