Meta-analysis: Metformin Treatment in Persons at Risk for Diabetes Mellitus

Abstract 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.