Efficacy and safety of sitagliptin when added to ongoing metformin therapy in patients with type 2 diabetes

Diabetes Obes Metab. 2008 Sep;10(10):959-69. doi: 10.1111/j.1463-1326.2007.00839.x. Epub 2008 Jan 14.

Abstract

Aim: To assess the addition of sitagliptin to ongoing metformin therapy in patients with type 2 diabetes who were inadequately controlled [haemoglobin A(1c) (HbA(1c)) 7-11%] on metformin monotherapy.

Methods: Patients (n = 273) on metformin (>/=1500 mg/day) were randomized to receive the addition of once-daily placebo, sitagliptin 100 mg or rosiglitazone 8 mg in a 1 : 1 : 1 ratio for 18 weeks. The efficacy analysis was based on the all-patients-treated population using an analysis of co-variance with change in HbA(1c) from baseline as the primary endpoint.

Results: The mean baseline HbA(1c) was 7.7% for the entire cohort. After 18 weeks, both active add-on therapies led to greater improvements in HbA(1c) from baseline: -0.73% for sitagliptin (p < 0.001 vs. placebo) and -0.79% for rosiglitazone compared with -0.22% for placebo. No difference was observed between the sitagliptin and rosiglitazone treatments (0.06% [95% confidence interval (CI): -0.14 to 0.25]). The proportion of patients achieving an HbA(1c) < 7% was greater with sitagliptin (55%) and rosiglitazone (63%) compared with placebo (38%). Body weight increased from baseline with rosiglitazone (1.5 kg) compared with body weight reduction with sitagliptin (-0.4 kg) and placebo (-0.8 kg). The difference in body weight between the sitagliptin and rosiglitazone groups was 1.9 kg (95% CI: 1.3-2.5). In a prespecified analysis, the proportion of patients experiencing a greater than 3-kg increase in body weight was 21% in the rosiglitazone group compared with 2% in both the sitagliptin and placebo groups. Both active treatments were generally well tolerated, with no increased risk of hypoglycaemia or gastrointestinal adverse events compared with placebo.

Conclusions: In this 18-week study, the addition of sitagliptin was effective and well tolerated in patients with type 2 diabetes inadequately controlled with metformin monotherapy. Treatment with sitagliptin produced similar reductions in HbA(1c) compared with the addition of rosiglitazone.

Publication types

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

MeSH terms

  • Analysis of Variance
  • Biomarkers / blood
  • Blood Glucose / analysis
  • Body Weight / drug effects
  • Cholesterol, LDL / blood
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin / analysis
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / blood
  • Lipids / blood
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Pyrazines / adverse effects
  • Pyrazines / therapeutic use*
  • Rosiglitazone
  • Sitagliptin Phosphate
  • Thiazolidinediones / adverse effects
  • Thiazolidinediones / therapeutic use
  • Treatment Outcome
  • Triazoles / adverse effects
  • Triazoles / therapeutic use*
  • Triglycerides / blood

Substances

  • Biomarkers
  • Blood Glucose
  • Cholesterol, LDL
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Lipids
  • Pyrazines
  • Thiazolidinediones
  • Triazoles
  • Triglycerides
  • Rosiglitazone
  • Metformin
  • Sitagliptin Phosphate