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

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.