Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes

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, 1,09 1 patients with type 2 diabetes and AIC 7.5-110/0 were randomized to one of six daily treatments: sitagliptin 100 mg/metformin 1,000 mg (S100/M1000 group), sitagiptin 100 mg/metformin 2,000 mg (S100/M2000 group), metformin 1,000 mg M1000 group), metformin 2,000 ring (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 AIC >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 S1008/M2000 for 24 weeks. RESULTS - The mean baseline AIC was 8.8% in the randomized patients. The placebo-subtracted AIC 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 h achieving an AlC <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 AIC 11.2%) treated with S100/M2000, the within-group mean AIC 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.