Meta-analysis: Metformin treatment in persons at risk for diabetes mellitus

PURPOSE: We performed a meta-analysis of randomized controlled trials to assess the effect of metformin on metabolic parameters and the incidence of new-onset diabetes in persons at risk for diabetes. METHODS: We performed comprehensive English- and non-English-language searches of EMBASE, MEDLINE, and CINAHL databases from 1966 to November of 2006 and scanned selected references. We included randomized trials of at least 8 weeks duration that compared metformin with placebo or no treatment in persons without diabetes and evaluated body mass index, fasting glucose, fasting insulin, calculated insulin resistance, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and the incidence of new-onset diabetes. RESULTS: Pooled results of 31 trials with 4570 participants followed for 8267 patient-years showed that metformin reduced body mass index (-5.3%, 95% confidence interval [CI], -6.7--4.0), fasting glucose (-4.5%, CI, -6.0--3.0), fasting insulin (-14.4%, CI, -19.9--8.9), calculated insulin resistance (-22.6%, CI, -27.3--18.0), triglycerides (-5.3%, CI, -10.5--0.03), and low-density lipoprotein cholesterol (-5.6%, CI, -8.3--3.0%), and increased high-density lipoprotein cholesterol (5.0%, CI, 1.6-8.3) compared with placebo or no treatment. The incidence of new-onset diabetes was reduced by 40% (odds ratio 0.6; CI, 0.5-0.8), with an absolute risk reduction of 6% (CI, 4-8) during a mean trial duration of 1.8 years. CONCLUSION: Metformin treatment in persons at risk for diabetes improves weight, lipid profiles, and insulin resistance, and reduces new-onset diabetes by 40%. The long-term effect on morbidity and mortality should be assessed in future trials. (C) 2008 Elsevier Inc. All rights reserved.