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

Diabetes Obes Metab. 2017 Nov;19(11):1602-1609. doi: 10.1111/dom.12988. Epub 2017 Jul 6.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Asian People
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage*
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Heterocyclic Compounds, 2-Ring / administration & dosage*
  • Heterocyclic Compounds, 2-Ring / adverse effects
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Japan
  • Male
  • Middle Aged
  • Placebos
  • Pyrans / administration & dosage*
  • Pyrans / adverse effects
  • Sitagliptin Phosphate / administration & dosage*
  • Sitagliptin Phosphate / adverse effects
  • Treatment Outcome

Substances

  • 2-(2,5-difluorophenyl)-5-(2-(methylsulfonyl)-2,6-dihydropyrrolo(3,4-c)pyrazol-5(4H)-yl)tetrahydro-2H-pyran-3-amine
  • Dipeptidyl-Peptidase IV Inhibitors
  • Heterocyclic Compounds, 2-Ring
  • Hypoglycemic Agents
  • Placebos
  • Pyrans
  • Sitagliptin Phosphate

Associated data

  • ClinicalTrials.gov/NCT01703221