Efficacy and Safety Comparison of Liraglutide, Glimepiride, and Placebo, All in Combination With Metformin, in Type 2 Diabetes

The LEAD (Liraglutide Effect and Action in Diabetes)-2 study

  1. Michael Nauck, MD, PHD1,
  2. Anders Frid, MD2,
  3. Kjeld Hermansen, MD3,
  4. Nalini S. Shah, MD4,
  5. Tsvetalina Tankova, MD5,
  6. Ismail H. Mitha, MD6,
  7. Milan Zdravkovic, MD, PHD7,
  8. Maria Düring, PHD7,
  9. David R. Matthews, MD8 and
  10. for the LEAD-2 Study Group
  1. 1Diabeteszentrum Bad Lauterberg, Harz, Germany
  2. 2Öresund Diabetes Team AB, Lund, Sweden
  3. 3Aarhus University Hospital, Aarhus, Denmark
  4. 4Seth G.S. Medical College and KEM Hospital, Mumbai, India
  5. 5Clinic of Diabetology, Sophia, Bulgaria
  6. 6Benmed Hospital, Benoni, Republic of South Africa
  7. 7Novo Nordisk, Bagsvaerd, Denmark
  8. 8Oxford Centre for Diabetes Endocrinology and Metabolism, Oxford, U.K.
  1. Corresponding author: Michael A. Nauck, nauck{at}diabeteszentrum.de

Abstract

OBJECTIVE—The efficacy and safety of adding liraglutide (a glucagon-like peptide-1 receptor agonist) to metformin were compared with addition of placebo or glimepiride to metformin in subjects previously treated with oral antidiabetes (OAD) therapy.

RESEARCH DESIGN AND METHODS—In this 26-week, double-blind, double-dummy, placebo- and active-controlled, parallel-group trial, 1,091 subjects were randomly assigned (2:2:2:1:2) to once-daily liraglutide (either 0.6, 1.2, or 1.8 mg/day injected subcutaneously), to placebo, or to glimepiride (4 mg once daily). All treatments were in combination therapy with metformin (1g twice daily). Enrolled subjects (aged 25–79 years) had type 2 diabetes, A1C of 7–11% (previous OAD monotherapy for ≥3 months) or 7–10% (previous OAD combination therapy for ≥3 months), and BMI ≤40 kg/m2.

RESULTS—A1C values were significantly reduced in all liraglutide groups versus the placebo group (P < 0.0001) with mean decreases of 1.0% for 1.8 mg liraglutide, 1.2 mg liraglutide, and glimepiride and 0.7% for 0.6 mg liraglutide and an increase of 0.1% for placebo. Body weight decreased in all liraglutide groups (1.8–2.8 kg) compared with an increase in the glimepiride group (1.0 kg; P < 0.0001). The incidence of minor hypoglycemia with liraglutide (∼3%) was comparable to that with placebo but less than that with glimepiride (17%; P < 0.001). Nausea was reported by 11–19% of the liraglutide-treated subjects versus 3–4% in the placebo and glimepiride groups. The incidence of nausea declined over time.

CONCLUSIONS—In subjects with type 2 diabetes, once-daily liraglutide induced similar glycemic control, reduced body weight, and lowered the occurrence of hypoglycemia compared with glimepiride, when both had background therapy of metformin.

Footnotes

  • Published ahead of print at http://care.diabetesjournals.org on 17 October 2008. Clinical trial reg. no. NCT00318461, clinicaltrials.gov.

  • *A complete list of the LEAD-2 study investigators can be found in an online appendix available at http://dx.doi.org/10.2337/dc08-1355.

  • Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

    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 September 28, 2008.
    • Received July 22, 2008.
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  1. Diabetes Care vol. 32 no. 1 84-90
  1. Online-Only Appendix
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