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

Objective: The purpose of this study was to evaluate the efficacy and safety of sitagliptin as an add-on to metformin therapy in patients with moderately severe (hemoglobin A1c ≥ 8.0% and ≤ 11.0%) type 2 diabetes mellitus (T2DM).Research design and methods: This was a multi­national, randomized, placebo-controlled, parallel-group, double-blind study conducted in 190 patients with T2DM. After ≥ 6 weeks of stable metformin monotherapy (≥ 1500 mg/day), patients were randomized to either the addition of sitagliptin 100 mg once daily or placebo to ongoing metformin for 30 weeks.Main outcome measures: The primary efficacy endpoint was reduction in hemoglobin A1c (HbA1c) measured after 18 weeks of sitagliptin treatment. Key secondary end­points included reduction in fasting plasma glucose (FPG) and 2-hour (2-h) postprandial plasma glucose (PPG) at 18 weeks, and HbA1c at 30 weeks. The proportion of patients meeting the goal of HbA1c < 7.0% was also analyzed.Results: Sitagliptin significantly reduced HbA1c, FPG, and 2-h PPG, compared with placebo (all p < 0.001). The net improvement in HbA1c was –1.0% at both 18 and 30 weeks, and a significantly greater proportion of patients treated with sitagliptin achieved HbA1c < 7.0% by the end of the study (22.1% vs. 3.3%, p < 0.001). Sitagliptin was well-tolerated. Compared with placebo, sitagliptin had a neutral effect on body weight and did not signif­icantly increase the risk of hypoglycemia or gastro­intestinal adverse events.Conclusions: Addition of sitagliptin 100 mg once daily to ongoing metformin therapy was well-tolerated and resulted in significant glycemic improvement in patients with moderately severe T2DM who were treated for 30 weeks.Trial registration: ClinicalTrials.gov identifier: NCT00337610.