The Efficacy and Safety of Saxagliptin When Added to Metformin Therapy in Patients With Inadequately Controlled Type 2 Diabetes With Metformin Alone

  1. Ralph A. DeFronzo, MD1,
  2. Miguel N. Hissa, MD2,
  3. Alan J. Garber, MD, PHD3,
  4. Jorge Luiz Gross, MD4,
  5. Raina Yuyan Duan, PHD5,
  6. Shoba Ravichandran, MD5,
  7. Roland S. Chen, MD5 and
  8. for the Saxagliptin 014 Study Group*
  1. 1University of Texas Health Science Center at San Antonio, San Antonio, Texas;
  2. 2Hospital Universitario Walter Cantidio, Fortaleza, Ceará, Brazil;
  3. 3Baylor College of Medicine, Houston, Texas;
  4. 4Centro De Pesquisa Em Diabetes, Porto Alegre, Rio Grande Do Sul, Brazil;
  5. 5Bristol-Myers Squibb Company, Princeton, New Jersey.
  1. Corresponding author: Ralph A. DeFronzo, albarado{at}uthscsa.edu.

Abstract

OBJECTIVE This 24-week trial assessed the efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes with inadequate glycemic control with metformin alone.

RESEARCH DESIGN AND METHODS This was a randomized, double-blind, placebo-controlled study of saxagliptin (2.5, 5, or 10 mg once daily) or placebo plus a stable dose of metformin (1,500–2,500 mg) in 743 patients (A1C ≥7.0 and ≤10.0%). Efficacy analyses were performed using an ANCOVA model using last observation carried forward methodology on primary (A1C) and secondary (fasting plasma glucose [FPG] and postprandial glucose [PPG] area under the curve [AUC]) end points.

RESULTS Saxagliptin (2.5, 5, and 10 mg) plus metformin demonstrated statistically significant adjusted mean decreases from baseline to week 24 versus placebo in A1C (−0.59, −0.69, and −0.58 vs. +0.13%; all P < 0.0001), FPG (−14.31, −22.03, and −20.50 vs. +1.24 mg/dl; all P < 0.0001), and PPG AUC (−8,891, −9,586, and −8,137 vs. −3,291 mg · min/dl; all P < 0.0001). More than twice as many patients achieved A1C <7.0% with 2.5, 5, and 10 mg saxagliptin versus placebo (37, 44, and 44 vs. 17%; all P < 0.0001). β-Cell function and postprandial C-peptide, insulin, and glucagon AUCs improved in all saxagliptin treatment groups at week 24. Incidence of hypoglycemic adverse events and weight reductions were similar to those with placebo.

CONCLUSIONS Saxagliptin once daily added to metformin therapy was generally well tolerated and led to statistically significant improvements in glycemic indexes versus placebo added to metformin in patients with type 2 diabetes inadequately controlled with metformin alone.

Footnotes

  • *A full list of investigators of the Saxagliptin 014 Study Group is available in an online appendix at http://care.diabetesjournals.org/cgi/content/full/dc08-1984/DC1.

  • Clinical trial reg. no. NCT00121667, clinicaltrials.gov.

  • 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.

    • Received November 3, 2008.
    • Accepted May 21, 2009.
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This Article

  1. Diabetes Care vol. 32 no. 9 1649-1655
  1. Online-Only Appendix
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