Efficacy and safety of the dipeptidyl peptidase-4 inhibitor gemigliptin compared with sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone

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 AUC_0-2h 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.