Author(s): Goldstein BJ, Feinglos MN, Lunceford JK, Johnson J, WilliamsHerman DE Sita
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Abstract OBJECTIVE: To assess the efficacy and safety of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes and inadequate glycemic control on diet and exercise. RESEARCH DESIGN AND METHODS: In a 24-week, randomized, double-blind, placebo-controlled, parallel-group study, 1,091 patients with type 2 diabetes and A1C 7.5-11\% were randomized to one of six daily treatments: sitagliptin 100 mg/metformin 1,000 mg (S100/M1000 group), sitagliptin 100 mg/metformin 2,000 mg (S100/M2000 group), metformin 1,000 mg (M1000 group), metformin 2,000 mg (M2000 group) (all as divided doses administered twice daily [b.i.d.]), sitagliptin 100 mg q.d. (S100 group), or placebo. Patients who had an A1C >11\% or a fasting glucose value >280 mg/dl after the run-in period were not eligible to be randomized; these patients could participate in an open-label substudy and were treated with S100/M2000 for 24 weeks. RESULTS: The mean baseline A1C was 8.8\% in the randomized patients. The placebo-subtracted A1C change from baseline was -2.07\% (S100/M2000), -1.57\% (S100/M1000), -1.30\% (M2000), -0.99\% (M1000), and -0.83\% (S100) (P < 0.001 for comparisons versus placebo and for coadministration versus respective monotherapies). The proportion of patients achieving an A1C <7\% and <6.5\% was 66 and 44\%, respectively, in the S100/M2000 group (P < 0.001 vs. S100 or M2000). For the open-label cohort (n = 117; baseline A1C 11.2\%) treated with S100/M2000, the within-group mean A1C change from baseline was -2.9\%. The incidence of hypoglycemia was low (0.5-2.2\%) across active treatment groups and not significantly different from that in the placebo group (0.6\%). The incidence of gastrointestinal adverse experiences was similar for coadministration therapies compared with their respective metformin monotherapy. CONCLUSIONS: The initial combination of sitagliptin and metformin provided substantial and additive glycemic improvement and was generally well tolerated in patients with type 2 diabetes.
This article was published in Diabetes Care
and referenced in Journal of Molecular and Genetic Medicine