A randomized placebo-controlled trial of metformin for the treatment of HIV lipodystrophy

Objective We conducted a randomized placebo-controlled trial to examine the effects of metformin on visceral adipose tissue (VAT), appendicular fat, lipid profile and insulin sensitivity in HIV-infected persons with central adiposity and mild insulin resistance. Methods Forty-eight HIV-infected men and women with a self-reported increase in abdominal girth and an abnormal waist-to-hip ratio were randomly assigned in double-blind fashion to receive metformin 1500 mg or placebo daily for 24 weeks. Persons with diabetes were excluded. The following measures were obtained at baseline and 24 weeks: single-slice computed tomography (CT) scan, dual-energy X-ray absorptiometry (DEXA), lipid profile and oral glucose tolerance test. Results The median fasting insulin concentration of all participants was 12.3 mu U/mL. The percentage change in VAT was not significantly different between the metformin and placebo groups in univariate analysis and linear regression analysis adjusting for age, height, baseline VAT and insulin area under the curve (10.1% vs 3.2%; P=0.58). Metformin was associated with a significant decrease in appendicular fat mass compared with placebo (-686.0 vs 161.0 g; P=0.03). There was no significant change in lipid profile or insulin sensitivity between the two groups at 24 weeks. Conclusion Metformin should be used with caution in the treatment of HIV lipodystrophy, and, if used, should be reserved for persons with adequate peripheral fat and marked insulin resistance.