Metformin in the Treatment of HIV Lipodystrophy Syndrome

CONTEXT: A syndrome of lipodystrophy, characterized by fat redistribution and insulin resistance, has been estimated to affect the majority of human immunodeficiency virus (HIV)-infected individuals who are treated with combination antiretroviral therapy. There are no proven therapies for the metabolic disturbances associated with HIV lipodystrophy syndrome. OBJECTIVE: To determine the safety and efficacy of metformin therapy in HIV-infected patients with fat redistribution and abnormal glucose homeostasis. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled pilot study conducted in a university hospital between December 1998 and January 2000. PATIENTS: Twenty-six HIV-infected, nondiabetic patients with fat redistribution and abnormal oral glucose tolerance test (OGTT) results, hyperinsulinemia, or both. INTERVENTIONS: Patients were randomly assigned to receive metformin, 500 mg twice daily (n = 14), or identical placebo (n = 12), for 3 months. MAIN OUTCOME MEASURES: Insulin area under the curve (AUC), calculated 120 minutes following a 75-g OGTT at baseline vs at 3-month follow-up and compared between treatment groups. RESULTS: Patients treated with metformin demonstrated significant reductions in mean (SEM) insulin AUC 120 minutes after OGTT (-2930 912 vs -414 432 microIU/mL -20349 6334 vs -2875 3000 pmol/L; P =.01), weight (-1.3 0.6 vs 1.1 0.4 kg; P =.005), and diastolic blood pressure (-5 4 vs 5 2 mm Hg; P =.009) vs controls, respectively. Metformin therapy was associated with a decrease in visceral abdominal fat (VAT; -1115 819 vs 1191 699 mm(2); P =.08) and a proportional reduction in subcutaneous abdominal fat (SAT); the VAT-SAT ratio was unchanged in metformin-treated vs placebo-treated patients. No increase in lactate or liver transaminase levels was observed with metformin treatment. Mild diarrhea was the most common adverse effect of metformin. No patient discontinued therapy because of adverse effects. CONCLUSIONS: This study suggests that a relatively low dosage of metformin reduces insulin resistance and related cardiovascular risk parameters in HIV-infected patients with lipodystrophy. JAMA. 2000;284:472-477