Diabetes Care, Vol 19, Issue 9 920-926, Copyright © 1996 by American Diabetes Association

ARTICLES

The effect of metformin on the metabolic abnormalities associated with upper-body fat distribution. BIGPRO Study Group

A Fontbonne, MA Charles, I Juhan-Vague, JM Bard, P Andre, F Isnard, JM Cohen, P Grandmottet, P Vague, ME Safar and E Eschwege
National Institute of Health and Medical Research, INSERM U21, Villejuif, France.

OBJECTIVE: The constellation of anomalies associated with insulin resistance is a plausible additional cause of ischemic cardiovascular disease and of NIDDM. To test this hypothesis in a primary prevention trial, the effects of metformin as a potential candidate for intervention in the insulin resistance syndrome (IRS) were evaluated in 324 middle-aged subjects with upper-body obesity. RESEARCH DESIGN AND METHODS: Trial patients were selected on the basis of a high waist-to-hip ratio. They were randomly allocated to receive either metformin or placebo, following a double-blind procedure. After 1 year of treatment, the main clinical and biological parameters of the IRS were assessed and their evolution compared between treatment groups. RESULTS: Compared with placebo, metformin induced a significant weight loss, a better maintenance of fasting blood glucose, total and LDL cholesterol levels, and a greater decrease of fasting plasma insulin concentration. Moreover, tissue-type plasminogen activator antigen, a marker of fibrinolytic impairment, showed a significant decrease under metformin. By contrast, metformin treatment had no significant effect on blood pressure or serum triglyceride and HDL cholesterol concentrations. The main side effect of metformin was diarrhea. CONCLUSIONS: The BIGuanides and Prevention of Risks in Obesity (BIGPRO1) results suggest that metformin would be a suitable candidate for long-term intervention for the prevention of diabetes but that its use in a trial of primary prevention of cardiovascular diseases requires either a reevaluation of its properties toward the most potentially atherogenic anomalies of the IRS or a better definition of the target population.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. R Desilets, S. Dhakal-Karki, and K. C Dunican Role of Metformin for Weight Management in Patients Without Type 2 Diabetes Ann. Pharmacother., June 1, 2008; 42(6): 817 - 826. [Abstract] [Full Text] [PDF]

				R.-R. Wu, J.-P. Zhao, X.-F. Guo, Y.-Q. He, M.-S. Fang, W.-B. Guo, J.-D. Chen, and L.-H. Li Metformin Addition Attenuates Olanzapine-Induced Weight Gain in Drug-Naive First-Episode Schizophrenia Patients: A Double-Blind, Placebo-Controlled Study Am J Psychiatry, March 1, 2008; 165(3): 352 - 358. [Abstract] [Full Text] [PDF]

				K. C Dunican, A. R Desilets, and J. K Montalbano Pharmacotherapeutic Options for Overweight Adolescents Ann. Pharmacother., September 1, 2007; 41(9): 1445 - 1455. [Abstract] [Full Text] [PDF]

				G. A. Bray and F. L. Greenway Pharmacological Treatment of the Overweight Patient Pharmacol. Rev., June 1, 2007; 59(2): 151 - 184. [Full Text] [PDF]

				E Webb and R Viner Should metformin be prescribed to overweight adolescents in whom dietary/behavioural modifications have not helped? Arch. Dis. Child., September 1, 2006; 91(9): 793 - 794. [Full Text] [PDF]

				K. M. Levri, E. Slaymaker, A. Last, J. Yeh, J. Ference, F. D'Amico, and S. A. Wilson Metformin as Treatment for Overweight and Obese Adults: A Systematic Review Ann. Fam. Med, September 1, 2005; 3(5): 457 - 461. [Abstract] [Full Text] [PDF]

				B. Kimmel and S. E. Inzucchi Oral Agents for Type 2 Diabetes: An Update Clin. Diabetes, April 1, 2005; 23(2): 64 - 76. [Abstract] [Full Text] [PDF]

				R. Padwal, S. R. Majumdar, J. A. Johnson, J. Varney, and F. A. McAlister A Systematic Review of Drug Therapy to Delay or Prevent Type 2 Diabetes Diabetes Care, March 1, 2005; 28(3): 736 - 744. [Abstract] [Full Text] [PDF]

				S Jadhav, J Petrie, W Ferrell, S Cobbe, and N Sattar Insulin resistance as a contributor to myocardial ischaemia independent of obstructive coronary atheroma: a role for insulin sensitisation? Heart, December 1, 2004; 90(12): 1379 - 1383. [Abstract] [Full Text] [PDF]

				S. L. Norris, X. Zhang, A. Avenell, E. Gregg, C. H. Schmid, C. Kim, and J. Lau Efficacy of Pharmacotherapy for Weight Loss in Adults With Type 2 Diabetes Mellitus: A Meta-analysis Arch Intern Med, July 12, 2004; 164(13): 1395 - 1404. [Abstract] [Full Text] [PDF]

				A. M Hess and D. L Sullivan Metformin for Prevention of Type 2 Diabetes Ann. Pharmacother., July 1, 2004; 38(7): 1283 - 1285. [Abstract] [Full Text] [PDF]

				B. Schultes, K. M. Oltmanns, W. Kern, H. L. Fehm, J. Born, and A. Peters Modulation of Hunger by Plasma Glucose and Metformin J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1133 - 1141. [Abstract] [Full Text] [PDF]

				M. Freemark Pharmacologic Approaches to the Prevention of Type 2 Diabetes in High Risk Pediatric Patients J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 3 - 13. [Full Text] [PDF]

				M. G. Wulffele, A. Kooy, P. Lehert, D. Bets, J. C. Ogterop, B. Borger van der Burg, A. J.M. Donker, and C. D.A. Stehouwer Combination of Insulin and Metformin in the Treatment of Type 2 Diabetes Diabetes Care, December 1, 2002; 25(12): 2133 - 2140. [Abstract] [Full Text] [PDF]

				S. Z. Yanovski and J. A. Yanovski Obesity N. Engl. J. Med., February 21, 2002; 346(8): 591 - 602. [Full Text] [PDF]

				S. E. Inzucchi Oral Antihyperglycemic Therapy for Type 2 Diabetes: Scientific Review JAMA, January 16, 2002; 287(3): 360 - 372. [Abstract] [Full Text] [PDF]

				B. Fruehwald-Schultes, W. Kern, K. M. Oltmanns, S. Sopke, B. Toschek, J. Born, H. L. Fehm, and A. Peters Metformin Does Not Adversely Affect Hormonal and Symptomatic Responses to Recurrent Hypoglycemia J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4187 - 4192. [Abstract] [Full Text] [PDF]

				M. Freemark and D. Bursey The Effects of Metformin on Body Mass Index and Glucose Tolerance in Obese Adolescents With Fasting Hyperinsulinemia and a Family History of Type 2 Diabetes Pediatrics, April 1, 2001; 107(4): e55 - e55. [Abstract] [Full Text] [PDF]

				J. M. Bard, M. A. Charles, I. Juhan-Vague, P. Vague, P. Andre, M. Safar, J. C. Fruchart, E. Eschwege, and o. b. o. t. BIGPRO Study Group Accumulation of Triglyceride-Rich Lipoprotein in Subjects With Abdominal Obesity : The Biguanides and the Prevention of the Risk of Obesity (BIGPRO) 1 Study Arterioscler. Thromb. Vasc. Biol., March 1, 2001; 21(3): 407 - 414. [Abstract] [Full Text] [PDF]

				G. A. Bray and F. L. Greenway Current and Potential Drugs for Treatment of Obesity Endocr. Rev., December 1, 1999; 20(6): 805 - 875. [Abstract] [Full Text]

				R. A. DeFronzo Pharmacologic Therapy for Type 2 Diabetes Mellitus Ann Intern Med, August 17, 1999; 131(4): 281 - 303. [Abstract] [Full Text] [PDF]

				J. D. Peuler Opposing adrenergic actions of intravenous metformin on arterial pressure in female spontaneously hypertensive rats Cardiovasc Res, July 1, 1999; 43(1): 237 - 247. [Abstract] [Full Text] [PDF]

				A. J Krentz Fortnightly Review: Insulin resistance BMJ, November 30, 1996; 313(7069): 1385 - 1389. [Abstract] [Full Text]