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

  1. Bernard Charbonnel, MD1,
  2. Avraham Karasik, MD2,
  3. Ji Liu, MA3,
  4. Mei Wu, MS3,
  5. Gary Meininger, MD3 and
  6. for the Sitagliptin Study 020 Group*
  1. 1Centre Hospitalier Universitaire de Nantes, Nantes, France
  2. 2Chaim Sheba Medical Center, Tel Hashomer, Israel
  3. 3Merck Research Laboratories, Rahway, New Jersey
  1. 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}


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 β-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.


  • B.C. has acted as a consultant or speaker for GlaxoSmithKline, Merck, Sharpe & Dohme, Pfizer, Sanofi-Aventis, and Takeda. A.K. has acted as a consultant or speaker for Merck Research Laboratories.

  • *

    * A complete list of the Study 620 investigators can be found in the online appendix at

  • A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

    • Accepted August 28, 2006.
    • Received March 31, 2006.
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