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Rhee E.J.,Sungkyunkwan University | Lee W.Y.,Sungkyunkwan University | Min K.W.,Eulji University | Shivane V.K.,Research Health Institute of Diabetes | And 6 more authors.
Diabetes, Obesity and Metabolism | Year: 2013

Aims: This study was designed to assess the efficacy and safety of a dipeptidyl peptidase-4 inhibitor, gemigliptin versus sitagliptin added to metformin in patients with type 2 diabetes. Methods: We conducted a double-blind, randomized, active-controlled trial in 425 Asian patients with inadequately controlled type 2 diabetes being treated with metformin alone. Eligible patients were randomized into three groups: 50mg gemigliptin qd, 25mg gemigliptin bid or sitagliptin 100mg qd added to ongoing metformin treatment for 24weeks. Haemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) were measured periodically, and oral glucose tolerance tests were performed at baseline and 24weeks after starting the treatment regimen. Results: Twenty-four weeks later, adding gemigliptin (50mg/day) to ongoing metformin therapy significantly improved glycaemic control. Reduction in HbA1c caused by 50mg gemigliptin qd (-0.77%±0.8) was non-inferior to that caused by 100mg sitagliptin qd (-0.8%±0.85). Proportion of patients achieving HbA1c <7% while taking 25mg gemigliptin bid (50%) or 50mg gemigliptin qd (54.07%) was comparable to the results with 100mg sitagliptin qd (48.87%). There were significant decreases in FPG, postprandial glucose and AUC0-2h glucose, as well as increases in GLP-1 and β cell sensitivity to glucose (supported by homeostasis model assessment of β-cell function, postprandial 2-h c-peptide and insulinogenic index) in patients receiving gemigliptin treatment with their metformin therapy. There was no increased risk of adverse effects with this dose of gemigliptin compared with sitagliptin 100mg qd. Conclusions: Addition of gemigliptin 50mg daily to metformin was shown to be efficacious, well tolerated and non-inferior to sitagliptin in patients with type 2 diabetes mellitus. © 2012 Blackwell Publishing Ltd.

Kumar A.,Diabetes Care and Research Center
Expert Opinion on Biological Therapy | Year: 2014

Introduction: Existing pharmacological therapies with basal insulins are limited by weight gain and hypoglycemia, while those with glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are limited by issues of efficacy when used alone. However, when used in combination they show a complementarity of action, in terms of reducing the incidence of hypoglycemia while providing sufficient glycemic control, that might help counterbalance their individual limitations. Clinical trials have demonstrated better efficacy and safety profile of this combination. Insulin degludec/liraglutide (IDegLira) is a once-daily fixed-dose combination of ultra-long-acting basal insulin degludec (IDeg) and GLP-1 RA, liraglutide. Areas covered: We reviewed published data regarding chemistry, pharmacokinetics, pharmacodynamics, clinical efficacy and safety of IDeg, liraglutide and the co-formulation. Literature was searched from the electronic medical database PubMed up to December 2013. Expert opinion: Preliminary studies on IDegLira indicate improved overall glycemic control, better safety profile with reduction in bodyweight and low rate of hypoglycemia compared to IDeg but higher rates of hypoglycemia than liraglutide therapy alone. Further, simplicity of fixed-dose combination offers an additional advantage of improved treatment adherence. IDegLira might be used similar to basal insulins in the current treatment algorithms, but with a greater preference for initiation instead of two or more oral drugs. © 2014 Informa UK, Ltd.

Kumar A.,Diabetes Care and Research Center
Diabetes/Metabolism Research and Reviews | Year: 2012

Following diagnosis, type 2 diabetic subjects are invariably treated with life style modifications and metformin. However, majority of these subjects require addition of another therapeutic agent singly or in combination; with or without insulin within few months to few years. For several decades, sulphonylureas and insulin have been the second line agent of choice. Clinical practice guidelines also suggest a similar approach. Subsequently thiazolidinediones, alpha glucose inhibitors and other agents were added to therapeutic armamentarium. Unfortunately, none of these treatment options could address the issue of progressive decline in beta cell function. Furthermore, they are responsible for unacceptable incidence of hypoglycaemia, weight gain and other side effects related to individual agents. Type 2 diabetic subjects have great propensity to develop cardiovascular complications. Sulphonylureas, insulin and thiazolidinediones have all been associated with adverse cardiovascular outcomes in differing magnitude. It has been made mandatory by regulatory agencies to ensure cardiovascular safety of any new anti-diabetic agent. Glucagon Like Peptide-1(GLP-1)-based therapies have been able to address several of these issues. Incretin mimetics and Di Peptidyl Dipeptidase IV (DPP-IV) inhibitors cause glucose-dependent insulin secretion and glucagon suppression from beta and alpha cells of the pancreas respectively. They owe this property to their binding with G-Protein-coupled receptors leading to an increased amount of c-AMP. They do not cause beta cell exhaustion. On the contrary such agents prevent beta cell apoptosis. Clinical trials have established the superiority of incretin mimetics particularly liraglutide against comparators including glimepiride, rosiglitazone and insulin Glargine in terms of efficacy. Furthermore, they have shown evidence towards beta cell protection, significant weight loss, minimal hypoglycaemia and favourable impact on surrogate markers of cardiovascular outcomes. DPP-IV inhibitors have limited ability to achieve glycaemic targets. However, they are weight neutral, cause minimal hypoglycaemia and have some beneficial effect on beta cell function. Finally, they are very well tolerated. © 2012 John Wiley & Sons, Ltd.

Kumar A.,Diabetes Care and Research Center | Sharma S.K.,MG Medical College | Rajput R.,PGIMS | Unnikrishnan A.G.,Amrita Institute of Medical science
Journal of Association of Physicians of India | Year: 2013

Biphasic insulin aspart 30 (BIAsp 30) has been used in patients for almost a decade; There is a wealth of knowledge from clinical trials to document its efficacy and safety and suggest that BIAsp 30 is an option for initiation and intensification of insulin therapy in patients with type 2 diabetes mellitus (T2DM). The A1chieve® was a non-interventional study that explored the safety and effectiveness of initiating or switching to insulin analogues in routine clinical practice in more than 60,000 patients from 28 different countries. In this manuscript, we discuss the findings from the subgroup of the Indian cohort who were treated with BIAsp 30. In a cohort of 15287 who were on BIAsp 30, 12645 (83%) were insulin naïve and 2642 (17%) had been on insulin therapy earlier. Glycaemic parameters were high at baseline. Mean (SD) HbA1c was 9.2% (1.3) in the these and was comparable in the insulin naïve and insulin experienced groups. After 24 weeks of therapy with BIAsp 30, there were reductions in HbA1c in both the insulin naïve group, [-1.8 (1.3)] and insulin experienced group [-1.6 (1.3)]. Fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels were also reduced significantly from baseline [-3.4 (2.7) and -4.8 (3.8) mmol/L, respectively, p< 0.05). Overall, hypoglycaemia decreased from 1.33 events/ patient years at baseline to 0.19 events/ patient years at 24 weeks. There was also an increase in quality of life score as evaluated by EQ-5D questionnaire. Initiating insulin therapy with or switching to BIAsp 30 in patients with poor glycaemic control leads to an improvement in glycaemic profile with no major hypoglycaemia or clinically significant weight gain. Therapy with BIAsp 30 also improves the quality of life in patients with type 2 diabetes. © SUPPLEMENT TO JAPI.

Russell-Jones D.,University of Surrey | Cuddihy R.M.,International Diabetes Center | Hanefeld M.,TU Dresden | Kumar A.,Diabetes Care and Research Center | And 4 more authors.
Diabetes Care | Year: 2012

OBJECTIVE - To test the safety and efficacy of exenatide once weekly (EQW) compared with metformin (MET), pioglitazone (PIO), and sitagliptin (SITA) over 26 weeks, in suboptimally treated (diet and exercise) drug-naive patients with type 2 diabetes. RESEARCH DESIGN AND METHODS - Patients were randomized to subcutaneous (SC) EQW 2.0 mg + oral placebo (n = 248), MET 2,000 mg/day + SC placebo (n = 246), PIO45 mg/day + SC placebo (n = 163), or SITA 100 mg/day + SC placebo (n = 163) for 26 weeks. MET and PIO therapies were increased to maximum-tolerated dosages. Injections with EQW or placebo were administered weekly, while oral medication or placebo was administered daily. RESULTS - Baseline characteristics were as follows: 59% men, 67% Caucasian, mean age 54 years, HbA1c 8.5%, fasting serum glucose 9.9 mmol/L, body weight 87.0 kg, and diabetes duration 2.7 years. HbA 1c reductions (%) at 26 weeks (least-squares means) with EQW versus MET, PIO, and SITA were -1.53 vs. -1.48 (P = 0.620), -1.63 (P = 0.328), and -1.15 (P < 0.001), respectively. Weight changes (kg) were -2.0 vs. -2.0 (P = 0.892), +1.5 (P < 0.001), and -0.8 (P < 0.001), respectively. Common adverse events were as follows: EQW, nausea (11.3%) and diarrhea (10.9%); MET, diarrhea (12.6%) and headache (12.2%); PIO, nasopharyngitis (8.6%) and headache (8.0%); and SIT, nasopharyngitis (9.8%) and headache (9.2%). Minor (confirmed) hypoglycemia was rarely reported. No major hypoglycemia occurred. CONCLUSIONS - EQW was noninferior to MET but not PIO and superior to SITA with regard to HbA1c reduction at 26 weeks. Of the agents studied, EQW and MET provided similar improvements in glycemic control along with the benefit of weight reduction and no increased risk of hypoglycemia. © 2012 by the American Diabetes Association.

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