Metformin in the Treatment of HIV Lipodystrophy Syndrome

Abstract

Research from JAMA — Metformin in the Treatment of HIV Lipodystrophy Syndrome — A Randomized Controlled Trial — ContextA 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.ObjectiveTo determine the safety and efficacy of metformin therapy in HIV-infected patients with fat redistribution and abnormal glucose homeostasis.Design and SettingRandomized, double-blind, placebo-controlled pilot study conducted in a university hospital between December 1998 and January 2000.PatientsTwenty-six HIV-infected, nondiabetic patients with fat redistribution and abnormal oral glucose tolerance test (OGTT) results, hyperinsulinemia, or both.InterventionsPatients were randomly assigned to receive metformin, 500 mg twice daily (n = 14), or identical placebo (n = 12), for 3 months.Main Outcome MeasuresInsulin 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.ResultsPatients treated with metformin demonstrated significant reductions in mean (SEM) insulin AUC 120 minutes after OGTT (−2930 [912] vs −414 [432] µIU/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] mm2; 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.ConclusionsThis study suggests that a relatively low dosage of metformin reduces insulin resistance and related cardiovascular risk parameters in HIV-infected patients with lipodystrophy.