Aim: To assess the addition of sitagliptin to ongoing metformin therapy in patients with type 2 diabetes who were inadequately controlled [haemoglobin A1c (HbA1c) 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 HbA1c from baseline as the primary endpoint.
Results: The mean baseline HbA1c was 7.7% for the entire cohort. After 18 weeks, both active add-on therapies led to greater improvements in HbA1c 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 HbA1c < 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 HbA1c compared with the addition of rosiglitazone.