Once-daily sitagliptin, a dipeptidyl peptidase-4 inhibitor, for the treatment of patients with type 2 diabetes

Curr Med Res Opin. 2007 Jun;23(6):1329-39. doi: 10.1185/030079907X188152. Epub 2007 Apr 30.


Objective: Sitagliptin, an oral, potent, and selective dipeptidyl peptidase-4 (DPP-4) inhibitor was evaluated as once-daily monotherapy in a 12-week randomized, double-blind, placebo-controlled, parallel group, dose-ranging study. Additionally, the glycemic response to sitagliptin 100 mg daily was evaluated as a once-daily (100 mg once-daily) or twice-daily (50 mg twice-daily) dosing regimen.

Research design and methods: In a multinational, double-blind, randomized, placebo-controlled, parallel-group, dose-range finding study, 555 patients, 23-74 years of age, with HbA(1c) of 6.5-10.0% were randomized to one of five treatment groups: placebo, sitagliptin 25, 50 or 100 mg once-daily, or sitagliptin 50 mg twice-daily for 12 weeks. The efficacy analysis was based on the all-patients-treated population using an ANCOVA model.

Results: Mean baseline HbA(1c) ranged from 7.6 to 7.8% across treatment groups, with 29% of all patients with values < or =7%. After 12 weeks, treatment with all doses of sitagliptin significantly (p < 0.05) reduced HbA(1c) by -0.39 to -0.56% and fasting plasma glucose by -11.0 to -17.2 mg/dL relative to placebo, with the greatest reduction observed in the 100-mg once-daily group. Mean daily glucose was significantly (p < 0.05) reduced by -14.0 to -22.6 mg/dL with all doses of sitagliptin relative to placebo. HOMA-beta was significantly (p < 0.05) increased by 11.3-15.2 with all sitagliptin doses relative to placebo. QUICKI and HOMA-IR were not significantly changed with sitagliptin treatment. There were no significant differences observed between the sitagliptin 100 mg once-daily and 50 mg twice-daily groups for any parameter. For sitagliptin, the incidence of adverse events of hypoglycemia was low, with one event in each of the 25- and 50-mg once-daily and 50-mg twice-daily treatment groups and two events in the 100 mg once-daily treatment group. There was no mean change in body weight with sitagliptin relative to placebo. Study duration may be a limitation because the extent of the glycemic response and the safety and tolerability may not have been fully elucidated in this 12-week study.

Conclusion: Sitagliptin monotherapy improved indices of glycemic control compared to placebo and was generally well-tolerated in patients with type 2 diabetes. The glycemic response to treatment with sitagliptin 100 mg/day was similar between the sitagliptin 100-mg once-daily and 50-mg twice-daily dose regimens.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / analysis
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage*
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Dosage Calculations
  • Female
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Male
  • Middle Aged
  • Placebos
  • Pyrazines / administration & dosage*
  • Pyrazines / adverse effects
  • Sitagliptin Phosphate
  • Treatment Outcome
  • Triazoles / administration & dosage*
  • Triazoles / adverse effects


  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Placebos
  • Pyrazines
  • Triazoles
  • hemoglobin A1c protein, human
  • Sitagliptin Phosphate