Effect of repaglinide addition to metformin monotherapy on glycemic control in patients with type 2 diabetes

OBJECTIVE - To compare the effect of repaglinide im combination with metfor min with monotherapy of each drug on glycemic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS - A total of 83 patients with type 2 diabetes w ho had inadequate glycemic control (HbA(1c) >7.1%) when receiving the antid iabetic agent metformin were enrolled in this multicenter, double-blind tri al. Subjects were randomized to continue with their prestudy dose of metfor min (n = 27), to continue with their prestudy dose of metformin with the ad dition of repaglinide (n = 27), or to receive repaglinide alone (n = 29). F or patients receiving repaglinide, the optimal dose was determined during a 4- to 8-week titration and continued for a 3-month maintenance period. RESULTS - In subjects receiving combined therapy, HbA(1c) was reduced by 1. 4 +/- 0.2%, from 8.3 to 6.9% (P = 0.0016) and fasting plasma glucose by 2.2 mmol/l (P = 0.0003). No significant changes were observed in subjects trea ted with either repaglinide or metformin monotherapy in HbA(1c) (0.4 and 0. 3% decrease, respectively) or fasting plasma glucose (0.5 mmol/l increase a nd 0.3 mmol/l decrease, respectively). Subjects receiving repaglinide, eith er alone or in combination with metformin, had an increase in fasting level s of insulin between baseline and the end of the trial of 4.04 +/- 1.56 and 4.23 +/- 1.50 mU/l, respectively (P < 0.02). Gastrointestinal adverse even ts were common in the metformin group. An increase in body weight occurred in the repaglinide and combined therapy groups (2.4 +/- 0.5 and 3.0 +/- 0.5 kg, respectively; P < 0.05). CONCLUSIONS - Combined metformin and repaglinide therapy resulted in superi or glycemic control compared with repaglinide or metformin monotherapy in p atients with type 2 diabetes whose glycemia had not been well controlled on metformin alone. Repaglinide monotherapy was as effective as metformin mon otherapy.