The Effect of Metformin and Intensive Lifestyle Intervention on the Metabolic Syndrome: The Diabetes Prevention Program Randomized Trial

  1. Trevor J. Orchard, MD;
  2. Marinella Temprosa, MS;
  3. Ronald Goldberg, MD;
  4. Steven Haffner, MD;
  5. Robert Ratner, MD;
  6. Santica Marcovina, PhD, DSc;
  7. Sarah Fowler, PhD; and
  8. for the Diabetes Prevention Program Research Group
  1. From the Diabetes Prevention Program Coordinating Center, The Biostatistics Center, George Washington University, Rockville, Maryland.

    Abstract

    Background: The metabolic syndrome is a high-risk state for diabetes and cardiovascular disease. Little is known about its prevalence and prevention in those with impaired glucose tolerance.

    Objective: To determine the prevalence of the metabolic syndrome at baseline in the Diabetes Prevention Program and the effect of intensive lifestyle intervention and metformin therapy on the syndrome's incidence and resolution.

    Design: Randomized, controlled clinical trial.

    Setting: Research and community-based centers.

    Participants: Participants had impaired glucose tolerance (World Health Organization criteria plus fasting plasma glucose level ≥5.3 mmol/L [≥95 mg/dL]) and were followed for a mean of 3.2 years after random assignment to intensive lifestyle intervention, metformin therapy, or placebo.

    Interventions: Metformin, 850 mg twice daily, or intensive lifestyle intervention designed to achieve and maintain a 7% weight loss and 150 minutes of exercise per week.

    Measurements: The metabolic syndrome was defined as having 3 or more characteristics (waist circumference; blood pressure; and levels of high-density lipoprotein cholesterol, triglycerides, and fasting plasma glucose) that met criteria from the National Cholesterol Education Program Adult Treatment Panel III.

    Results: Fifty-three percent of participants (n = 1711) had the metabolic syndrome at baseline; incidence did not vary substantially by age. However, low levels of high-density lipoprotein cholesterol predominated in younger participants (age 25 to 44 years), and high blood pressure predominated in older participants (age 60 to 82 years). In life-table analyses (log-rank test), incidence of the metabolic syndrome was reduced by 41% in the lifestyle group (P < 0.001) and by 17% in the metformin group (P = 0.03) compared with placebo. Three-year cumulative incidences were 51%, 45%, and 34% in the placebo, metformin, and lifestyle groups, respectively. There was no significant heterogeneity by ethnic group.

    Limitations: The study involved a volunteer group with impaired glucose tolerance, which limits generalizability.

    Conclusions: The metabolic syndrome affected approximately half of the participants in the Diabetes Prevention Program at baseline. Both lifestyle intervention and metformin therapy reduced the development of the syndrome in the remaining participants.

    Article and Author Information

    • Grant Support: Funding was provided by the National Institutes of Health (5U01DK048489) through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center on Minority Health and Health Disparities, the National Institute of Child Health and Human Development, the Office of Women's Health, and the National Institute on Aging. In addition, the Indian Health Service, the Centers for Disease Control and Prevention, the American Diabetes Association, and 2 pharmaceutical companies—Bristol-Myers Squibb and Parke-Davis—contributed support. The General Clinical Research Center Program, National Center for Research Resources, supported many of the clinical centers. Support to the clinical centers and the Coordinating Center was provided by the National Institute of Diabetes and Digestive and Kidney Diseases through a cooperative agreement, except for the Southwestern American Indian Centers, which were supported directly by the National Institute of Diabetes and Digestive and Kidney Diseases and the Indian Health Service.

    • Potential Financial Conflicts of Interest: Consultancies: T.J. Orchard (Metabolic Syndrome Alliance, Sanofi-Aventis); Grants received: R. Ratner (Bristol-Myers Squibb).

    • Requests for Single Reprints: Diabetes Prevention Program Coordinating Center, The Biostatistics Center, George Washington University, 6110 Executive Boulevard, Suite 750, Rockville, MD 20852.

    • Current Author Addresses: Dr. Orchard: Diabetes and Lipid Research Building, University of Pittsburgh, 3512 5th Avenue 203, Pittsburgh, PA 15213.

    • Ms. Temprosa and Dr. Fowler: George Washington University, Biostatistics Center, 6110 Executive Boulevard, Suite 750, Rockville, MD 20852.

    • Dr. Goldberg: Diabetes Research Institute, University of Miami School of Medicine, 1450 NW 10th Avenue R-77, Miami, FL 33136.

    • Dr. Haffner: Department of Medicine, Clinical Epidemiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MSC 7873, San Antonio, TX 78229-3900.

    • Dr. Ratner: Medstar Research Institute, 6495 New Hampshire Avenue, Suite 201, Hyattsville, MD 20783.

    • Dr. Marcovina: Northwest Lipid Research Labs, 2121 North 35th Street, University of Washington, Seattle, WA 98103-9103.

    • Author Contributions: Conception and design: T.J. Orchard, M. Temprosa, R. Goldberg, S. Haffner, R. Ratner, S. Fowler.

    • Analysis and interpretation of the data: T.J. Orchard, M. Temprosa, R. Goldberg, R. Ratner, S. Fowler.

    • Drafting of the article: T.J. Orchard, M. Temprosa, R. Goldberg, S. Haffner, S. Fowler.

    • Critical revision of the article for important intellectual content: T.J. Orchard, M. Temprosa, R. Goldberg, S. Haffner, R. Ratner, S. Marcovina, S. Fowler.

    • Final approval of the article: T.J. Orchard, M. Temprosa, R. Goldberg, R. Ratner, S. Marcovina, S. Fowler.

    • Provision of study materials or patients: The DPP Research Group, T.J. Orchard, R. Goldberg, S. Haffner, R. Ratner, S. Marcovina.

    • Statistical expertise: M. Temprosa, S. Fowler.

    • Obtaining of funding: The DPP Research Group Principal Investigators.

    • Administrative, technical, or logistic support: T.J. Orchard, M. Temprosa, R. Goldberg, S. Marcovina, S. Fowler.

    • Collection and assembly of data: The DPP Research Group, T.J. Orchard, M. Temprosa, R. Goldberg.

    Responses to this article

    • In Response
      • Trevor J Orchard and
      • Marinella Temprosa and Robert Ratner
      Ann Intern Med published online October 26, 2009
    • Sleep Related Breathing Disorders and the Metabolic Syndrome
      • PRISCILLA S. SARINAS M.D. FACP and
      • Daniel S. Dube, M.D.
      Ann Intern Med published online October 26, 2009
    • Multitargeted treatment for metabolic syndrome
      • Vasilios G Athyros and
      • Dimitri P. Mikhailidis, and Moses Elisaf
      Ann Intern Med published online October 26, 2009
    • Metabolic Syndrome and Fatty Liver
      • Frank A. Anania and
      • Samir Parekh, Aasma Shaukat
      Ann Intern Med published online October 26, 2009

    Summary for Patients

    • Summaries for Patients:The Effect of Diet and Exercise or Metformin on the Metabolic Syndrome Ann Intern Med April 19, 2005 142:I-46
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    1. Ann Intern Med April 19, 2005 vol. 142 no. 8 611-619
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