Randomized clinical trial of the safety and efficacy of sitagliptin and metformin co-administered to Chinese patients with type 2 diabetes mellitus

J Diabetes Investig. 2016 Sep;7(5):727-36. doi: 10.1111/jdi.12511. Epub 2016 May 19.

Abstract

Introduction: The results of a clinical trial to evaluate the efficacy and safety of initial combination therapy with sitagliptin and metformin in Chinese patients with type 2 diabetes and inadequate glycemic control are reported here.

Materials and methods: This was a multicenter, randomized, double-blind, placebo-controlled, parallel group, 24-week clinical trial carried out in China. Patients (n = 744) with type 2 diabetes and inadequate glycemic control (glycated hemoglobin ≥7.5 and ≤11.0%) who were either drug-naïve or washed out of previous therapy were randomized in equal ratios to sitagliptin 100 mg once daily (q.d.; S100), metformin 500 mg twice daily (b.i.d.; M1000), metformin 850 mg b.i.d. (M1700), sitagliptin 50 mg b.i.d. plus metformin 500 mg b.i.d. (S100/M1000), sitagliptin 50 mg b.i.d. plus metformin 850 mg b.i.d. (S100/M1700), or placebo.

Results: The mean baseline glycated hemoglobin in randomized patients was 8.7%. Least squares mean changes from baseline in glycated hemoglobin were -0.59% (placebo), -0.99% (S100), -1.29% (M1000), -1.56% (M1700), -1.67% (S100/M1000) and -1.83% (S100/M1700) (P < 0.05 for each active group vs placebo, for S100/M1700 and S100/M1000 vs S100, and for S100/M1000 vs M1000). All treatments were generally well-tolerated. The overall incidence of hypoglycemia (symptomatic or asymptomatic) was higher in the two co-administration groups (S100/M1700 and S100/M1000) compared with the placebo. The incidence of symptomatic hypoglycemia was low, and similar, across all treatment groups. The incidences of gastrointestinal adverse events were generally higher in high-dose metformin groups than in the placebo group.

Conclusions: In Chinese patients with type 2 diabetes, initial combination therapy with sitagliptin and metformin was generally well-tolerated, and provided improvement in glycemic control.

Keywords: Dipeptidyl peptidase-4 inhibitor; Glycemic control; Incretin therapy.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • China
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Metformin / administration & dosage
  • Metformin / adverse effects
  • Metformin / therapeutic use*
  • Middle Aged
  • Sitagliptin Phosphate / administration & dosage
  • Sitagliptin Phosphate / adverse effects
  • Sitagliptin Phosphate / therapeutic use*
  • Treatment Outcome

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • hemoglobin A1c protein, human
  • Metformin
  • Sitagliptin Phosphate