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Diabetes Care 29:2638-2643, 2006
DOI: 10.2337/dc06-0706
© 2006 by the American Diabetes Association
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Emerging Treatments and Technologies
Original Article

Efficacy and Safety of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Added to Ongoing Metformin Therapy in Patients With Type 2 Diabetes Inadequately Controlled With Metformin Alone

Bernard Charbonnel, MD1, Avraham Karasik, MD2, Ji Liu, MA3, Mei Wu, MS3, Gary Meininger, MD3 for the Sitagliptin Study 020 Group*

1 Centre Hospitalier Universitaire de Nantes, Nantes, France
2 Chaim Sheba Medical Center, Tel Hashomer, Israel
3 Merck Research Laboratories, Rahway, New Jersey

Address correspondence and reprint requests to Gary Meininger, MD, Director, Clinical Research, Merck Research Laboratories, 126 E. Lincoln Ave., RY34A-254, Rahway, NJ 07065. E-mail: gary_meininger{at}merck.com

OBJECTIVE—The efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, added to ongoing metformin therapy, were assessed in patients with type 2 diabetes who had inadequate glycemic control (HbA1c [A1C] ≥7 and ≤10%) with metformin alone.

RESEARCH DESIGN AND METHODS—After a screening diet/exercise run-in period, a metformin dose titration/stabilization period, and a 2-week, single-blind, placebo run-in period, 701 patients, aged 19–78 years, with mild to moderate hyperglycemia (mean A1C 8.0%) receiving ongoing metformin (≥1,500 mg/day) were randomly assigned to receive the addition of placebo or sitagliptin 100 mg once-daily in a 1:2 ratio for 24 weeks. Patients exceeding specific glycemic limits were provided rescue therapy (pioglitazone) until the end of the study. The efficacy analyses were based on an all-patients-treated population using an ANCOVA and excluded data obtained after glycemic rescue.

RESULTS—At week 24, sitagliptin treatment led to significant reductions compared with placebo in A1C (–0.65%), fasting plasma glucose, and 2-h postmeal glucose. Fasting insulin, fasting C-peptide, fasting proinsulin-to-insulin ratio, postmeal insulin and C-peptide areas under the curve (AUCs), postmeal insulin AUC–to–glucose AUC ratio, homeostasis model assessment of ß-cell function, and quantitative insulin sensitivity check index were significantly improved with sitagliptin relative to placebo. A significantly greater proportion of patients achieved an A1C <7% with sitagliptin (47.0%) than with placebo (18.3%). There was no increased risk of hypoglycemia or gastrointestinal adverse experiences with sitagliptin compared with placebo. Body weight decreased similarly with sitagliptin and placebo.

CONCLUSIONS—Sitagliptin 100 mg once-daily added to ongoing metformin therapy was efficacious and well tolerated in patients with type 2 diabetes who had inadequate glycemic control with metformin alone.

Abbreviations: AUC, area under the curve • DPP-4, dipeptidyl peptidase-4 • ECG, electrocardiogram • FPG, fasting plasma glucose • GIP, glucose-dependent insulinotropic peptide • GLP-1, glucagon-like peptide-1 • HOMA-ß, homeostasis model assessment of ß-cell function • HOMA-IR, homeostasis model assessment of insulin resistance • OHA, oral antihyperglycemic agent • QUICKI, quantitative insulin sensitivity check index


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