Efficacy and safety of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes: a 54-week study

OBJECTIVE: To assess the 54-week efficacy and safety of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes and inadequate glycemic control (HbA(1c) 7.5-11%) on diet and exercise. METHODS AND MATERIALS: This was multinational study conducted at 140 clinical sites in 18 countries. Following an initial 24-week, double-blind, placebo-controlled period, patients entered a double-blind continuation period for an additional 30 weeks. Following the week 24 evaluation, patients remained on their previously assigned active, oral treatments: sitagliptin 50 mg b.i.d. + metformin 1000 mg b.i.d. (S100 + M2000), sitagliptin 50 mg b.i.d. + metformin 500 mg b.i.d. (S100 + M1000), metformin 1000 mg b.i.d. (M2000), metformin 500 mg b.i.d. (M1000), and sitagliptin 100 mg q.d. (S100). Patients initially randomized to placebo were switched to M2000 (designated PBO/M2000) at week 24. This report summarizes the overall safety and tolerability data for the 54-week study and presents efficacy results for patients randomized to continuous treatments who entered the 30-week continuation period. RESULTS: Of the 1091 randomized patients, 906 completed the 24-week placebo-controlled phase and 885 patients continued into the 30-week continuation period (S100 + M2000 n = 161, S100+M1000 n = 160, M2000 n = 153, M1000 n = 147, S100 n = 141, PBO/M2000 n = 123). At baseline, patients included in the efficacy analysis had mean age of 54 years, mean BMI of 32 kg/m(2), mean HbA(1c) of 8.7% (8.5-8.8% across groups), and mean duration of type 2 diabetes of 4 years. At week 54, in the all-patients-treated analysis of continuing patients, least-squares (LS) mean changes in HbA(1c) from baseline were -1.8% (S100 + M2000), -1.4% (S100 + M1000), -1.3% (M2000), -1.0% (M1000), and -0.8% (S100). The proportions of continuing patients with an HbA(1c) 8% after week 24, there was a greater likelihood of glycemic rescue in the monotherapy groups; this led to more missing data in the continuation all-patients-treated population(CAPT) analysis and fewer patients contributing to the completers analysis in the monotherapy groups. CONCLUSIONS: In this study, initial treatment with sitagliptin, metformin, or the combination therapy of sitagliptin and metformin provided substantial and durable glycemic control, improved markers of beta-cell function, and was generally well-tolerated over 54 weeks in patients with type 2 diabetes.