Efficacy and safety of sitagliptin and metformin as initial combination therapy and as monotherapy over 2 years in patients with type 2 diabetes

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2010-05, Vol.12 (5), p.442-451
• Main Authors: Williams-Herman, D, Johnson, J, Teng, R, Golm, G, Kaufman, K.D, Goldstein, B.J, Amatruda, J.M
• Format: Article
• Language: English
• Subjects: Antidiabetics; Beta cells; biguanides; Body Mass Index; Combination therapy; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; dipeptidyl peptidase-4; Double-Blind Method; Drug Therapy, Combination; Female; Glycated Hemoglobin A - analysis; Humans; Hypoglycemia; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - pharmacology; incretins; Male; Metformin; Metformin - administration & dosage; Metformin - pharmacology; Middle Aged; Placebos; Pyrazines - administration & dosage; Pyrazines - pharmacology; Sitagliptin Phosphate; Treatment Outcome; Triazoles - administration & dosage; Triazoles - pharmacology
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/j.1463-1326.2010.01204.x

Aim: To assess the 104-week efficacy and safety of sitagliptin and metformin as initial combination therapy and as monotherapy in patients with type 2 diabetes and inadequate glycaemic control (HbA₁c 7.5-11%) on diet and exercise. Methods: This study was a 50-week, double-blind extension of a 54-week, randomized, double-blind, factorial study of the initial combination of sitagliptin and metformin, metformin monotherapy and sitagliptin monotherapy (104 weeks total duration). Patients assigned to active therapy in the 54-week base study remained on those treatments in the extension study: sitagliptin 50 mg b.i.d. + metformin 1000 mg b.i.d. (higher dose combination), sitagliptin 50 mg b.i.d. + metformin 500 mg b.i.d. (lower dose combination), metformin 1000 mg b.i.d. (higher dose), metformin 500 mg b.i.d. (lower dose) and sitagliptin 100 mg q.d. Patients randomized to receive the sequence of placebo/metformin were switched, in a blinded manner, from placebo to metformin monotherapy uptitrated to 1000 mg b.i.d. beginning at week 24 and remained on higher dose metformin through the extension. Results: Amongst patients who entered the extension study without having initiated glycaemic rescue therapy, least-squares mean changes in HbA₁c from baseline at week 104 were -1.7% (higher dose combination), -1.4% (lower dose combination), -1.3% (higher dose), -1.1% (lower dose) and -1.2% (sitagliptin). The proportions of patients with an HbA₁c