Factors Associated With Diabetes Onset During Metformin Versus Placebo Therapy in the Diabetes Prevention Program
Open Access
- 1 April 2007
- journal article
- research article
- Published by American Diabetes Association in Diabetes
- Vol. 56 (4), 1153-1159
- https://doi.org/10.2337/db06-0918
Abstract
In the Diabetes Prevention Program, treatment of subjects with impaired glucose tolerance with metformin >3.2 years reduced the risk of developing type 2 diabetes by 30% compared with placebo. This study describes the mechanisms of this effect. In proportional hazards regression models with 2,155 subjects, changes in weight, the insulinogenic index (IGR), fasting insulin, and proinsulin were predictive of diabetes, though to different degrees within each group. The mean change in weight, fasting insulin, and proinsulin, but not IGR, differed between groups during the study. The 1.7-kg weight loss with metformin versus a 0.3-kg gain with placebo alone explained 64% of the beneficial metformin effect on diabetes risk. Adjustment for weight, fasting insulin, proinsulin, and other metabolic factors combined explained 81% of the beneficial metformin effect, but it remained nominally significant (P = 0.034). After the addition of changes in fasting glucose, 99% of the group effect was explained and is no longer significant. Treatment of high-risk subjects with metformin results in modest weight loss and favorable changes in insulin sensitivity and proinsulin, which contribute to a reduction in the risk of diabetes apart from the associated reductions in fasting glucose.Keywords
This publication has 26 references indexed in Scilit:
- Effect of Weight Loss With Lifestyle Intervention on Risk of DiabetesDiabetes Care, 2006
- Dietary intake in the Diabetes Prevention Program cohort: baseline and 1-year post-randomizationAnnals of Epidemiology, 2004
- Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or MetforminNew England Journal of Medicine, 2002
- Evaluation of Simple Indices of Insulin Sensitivity and Insulin Secretion for Use in Epidemioiogic StudiesAmerican Journal of Epidemiology, 2000
- Release of incompletely processed proinsulin is the cause of the disproportionate proinsulinemia of NIDDMDiabetes, 1997
- Introduction to a Collection of Physical Activity QuestionnairesMedicine & Science in Sports & Exercise, 1997
- Metabolic effects of metformin on glucose and lactate metabolism in noninsulin-dependent diabetes mellitusJournal of Clinical Endocrinology & Metabolism, 1996
- Exercise training improves functional status in patients with peripheral arterial diseaseJournal of Vascular Surgery, 1996
- Understanding Oral Glucose Tolerance: Comparison of Glucose or Insulin Measurements During the Oral Glucose Tolerance Test with Specific Measurements of Insulin Resistance and Insulin SecretionDiabetic Medicine, 1994
- Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic functionDiabetes, 1993