Journal Article

Effect of Initial Combination Therapy With Sitagliptin, a Dipeptidyl Peptidase-4 Inhibitor, and Metformin on Glycemic Control in Patients With Type 2 Diabetes

Lunceford, Jared K, Goldstein, Barry J, Feinglos, Mark N, Williams-Herman, Debora E, Johnson, Jeremy

2007

Overview

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.

• Publisher: American Diabetes Association
• Subject: Adult / Aged / analysis / Biological and medical sciences / blood / Blood Glucose / Blood Glucose - drug effects / Blood Glucose - metabolism / Clinical trials / Diabetes / Diabetes Mellitus, Type 2 / Diabetes Mellitus, Type 2 - blood / Diabetes Mellitus, Type 2 - drug therapy / Diabetes. Impaired glucose tolerance / diet / Dose-Response Relationship, Drug / Double-Blind Method / drug effects / Drug therapy / Drug Therapy, Combination / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Etiopathogenesis. Screening. Investigations. Target tissue resistance / exercise / fasting / Feeding. Feeding behavior / Fundamental and applied biological sciences. Psychology / gastrointestinal system / glucose / Glycated Hemoglobin / Glycated Hemoglobin A - analysis / glycemic control / Humans / Hyperglycemia / Hypoglycemia / Hypoglycemic Agents / Hypoglycemic Agents - therapeutic use / Medical sciences / metabolism / metformin / Metformin - therapeutic use / Methods / Middle Aged / noninsulin-dependent diabetes mellitus / Patient Selection / patients / Placebos / Pyrazines / Pyrazines - therapeutic use / Single-Blind Method / Sitagliptin Phosphate / therapeutic use / therapeutics / Triazoles / Triazoles - therapeutic use / Type 2 diabetes / Vertebrates: anatomy and physiology, studies on body, several organs or systems / Vertebrates: endocrinology