A randomized, placebo- and sitagliptin-controlled trial of the safety and efficacy of omarigliptin, a once-weekly dipeptidyl peptidase-4 inhibitor, in Japanese patients with type 2 diabetes

Ira Gantz, Taro Okamoto, Yuka Ito, Kotoba Okuyama, Edward A O'Neill, Keith D Kaufman, Samuel S Engel, Eseng Lai, the Omarigliptin Study 020 Group, Ira Gantz, Taro Okamoto, Yuka Ito, Kotoba Okuyama, Edward A O'Neill, Keith D Kaufman, Samuel S Engel, Eseng Lai, the Omarigliptin Study 020 Group

Abstract

Aims: To assess the safety and efficacy of omarigliptin in Japanese patients with type 2 diabetes (T2D).

Methods: In a 24-week double-blind trial, 414 patients with T2D were randomized to omarigliptin 25 mg once weekly, sitagliptin 50 mg once daily or placebo. The double-blind period was followed by a 28-week open-label extension during which all patients received omarigliptin 25 mg once weekly. Efficacy endpoints were glycated haemoglobin (HbA1c), 2-hour postprandial glucose (PPG) and fasting plasma glucose (FPG) levels.

Results: After 24 weeks, the least squares (LS) mean change from baseline in HbA1c was -0.66% for omarigliptin, -0.65% for sitagliptin and 0.13% for placebo. The difference in LS mean for omarigliptin vs placebo was -0.80% ( P < .001). The difference in LS mean for omarigliptin vs sitagliptin was -0.02% (95% confidence interval -0.15, 0.12), which met the criterion for non-inferiority to sitagliptin. Both active treatments provided significant reductions in FPG and 2-hour PPG compared with placebo (P < .001). Over the 24-week double-blind period, there were no clinically meaningful differences in the incidence rates of adverse events among the treatment groups. There was 1 episode of symptomatic hypoglycaemia in the sitagliptin group and none in the omarigliptin or placebo groups. In the 28-week open-label period, omarigliptin provided persistent improvements in glycaemic control without notable change in safety profile compared with the double-blind period. Omarigliptin had no meaningful effect on body weight.

Conclusions: In Japanese patients with T2D, omarigliptin 25 mg once weekly provided significant glucose-lowering compared with placebo and was non-inferior to sitagliptin 50 mg once daily. Omarigliptin was generally well tolerated for up to 52 weeks.

Trial registration: ClinicalTrials.gov NCT01703221.

Keywords: MK-3102; incretins; oral antihyperglycaemic agent.

Conflict of interest statement

All authors are employees of MSD K.K. or Merck Sharp & Dohme Corp., subsidiaries of Merck & Co., Inc., Kenilworth, New Jersey, who may own stock and/or hold stock options in the Company.

© 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Efficacy measures up to week 24; A, HbA1c; B, FPG; (black triangles, placebo; white squares, sitagliptin; black circles, omarigliptin; based on an LDA model with terms for treatment, prior AHA therapy status (yes/no), time, and interaction of time by treatment, time by prior AHA therapy status, and time by treatment by prior AHA therapy status, with the constraint that the mean baseline was the same for all treatment groups). s.e., standard error
Figure 2
Figure 2
Percentage of patients at HbA1c goals of 7.0% or 6.5% at week 24. P values are associated with differences of active treatment groups from placebo

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