title: Safety and Efficacy of Omarigliptin (MK-3102), a Novel Once-Weekly DPP-4 Inhibitor for the Treatment of Patients With Type 2 Diabetes.
abstract: OBJECTIVE
  This study was conducted to determine the optimal dose of omarigliptin, a once-weekly (q.w.) dipeptidyl peptidase IV (DPP-4) inhibitor, for the treatment of patients with type 2 diabetes and evaluate the long-term safety of that dose.
  
  
  METHODS
  In a multicenter, double-blind, 12-week, dose-range finding study, 685 oral antihyperglycemic agent-naïve or washed-out subjects with type 2 diabetes were randomized to one of five once-weekly doses of omarigliptin (0.25 mg, 1 mg, 3 mg, 10 mg, or 25 mg) or placebo. The primary efficacy end point was change from baseline in HbA1c, and secondary end points were 2-h postmeal glucose (PMG) and fasting plasma glucose (FPG). Analysis included all patients who received at least one dose of the study medication. Subjects who completed the base study were eligible to enter a 66-week extension study.
  
  
  RESULTS
  Once-weekly treatment for 12 weeks with omarigliptin provided dose-related reductions in HbA1c, 2-h PMG, and FPG. At week 12, the omarigliptin 25-mg dose provided the greatest glycemic efficacy. The placebo-adjusted least-squares mean reductions from baseline in HbA1c, 2-h PMG, and FPG were -0.72% (-7.8 mmol/mol), -2.5, and -1.3 mmol/L, respectively (all P < 0.001). The incidence of adverse events was similar across dose groups, with a low incidence of symptomatic hypoglycemia and no effect on body weight. Omarigliptin was generally well-tolerated throughout the base and extension studies.
  
  
  CONCLUSIONS
  Omarigliptin 25 mg q.w., compared with placebo, provided significant glucose lowering and was generally well tolerated for up to 78 weeks in patients with type 2 diabetes.
authors: Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan; and College of Medicine, National Defense Medical Center, Taipei, Taiwan.
authors: Wayne H-H
authors: WH
authors: Sheu
authors: Merck & Co., Inc., Kenilworth, NJ ira.gantz@merck.com.
authors: Ira
authors: I
authors: Gantz
authors: Merck & Co., Inc., Kenilworth, NJ.
authors: Menghui
authors: M
authors: Chen
authors: Merck & Co., Inc., Kenilworth, NJ.
authors: Shailaja
authors: S
authors: Suryawanshi
authors: Merck & Co., Inc., Kenilworth, NJ.
authors: Arpana
authors: A
authors: Mirza
authors: Merck & Co., Inc., Kenilworth, NJ.
authors: Barry J
authors: BJ
authors: Goldstein
authors: Merck & Co., Inc., Kenilworth, NJ.
authors: Keith D
authors: KD
authors: Kaufman
authors: Merck & Co., Inc., Kenilworth, NJ.
authors: Samuel S
authors: SS
authors: Engel
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006574:Heterocyclic Compounds, 2-Ring / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011714:Pyrans / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: C587539:2-(2,5-difluorophenyl)-5-(2-(methylsulfonyl)-2,6-dihydropyrrolo(3,4-c)pyrazol-5(4H)-yl)tetrahydro-2H-pyran-3-amine; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006574:Heterocyclic Compounds, 2-Ring; D007004:Hypoglycemic Agents; D011714:Pyrans