Leptin replacement improves postprandial glycemia and insulin sensitivity in human immunodeficiency virus-infected lipoatrophic men treated with pioglitazone: a pilot study

Abstract

Highly active antiretroviral therapy (HAART)-induced lipoatrophy is characterized by hypoleptinemia and insulin resistance. Evidence suggests that pioglitazone and recombinant methionyl human leptin (metreleptin) administration has beneficial effects in human immunodeficiency virus (HIV)-infected lipoatrophic patients. This proof-of-concept study aimed at evaluating whether the combination of metreleptin and pioglitazone has favorable effects, above and beyond pioglitazone alone, on both metabolic outcomes and peripheral lipoatrophy in HIV-infected patients on HAART. Nine HIV-positive men with at least 6 months of HAART exposure, clinical evidence of lipoatrophy, and low leptin concentrations (≤4 ng/mL) were placed on pioglitazone treatment (30 mg/d per os) and were randomized to receive either metreleptin (0.04 mg/kg subcutaneously once daily; n = 5) or placebo (n = 4) for 3 months in a double-blinded fashion. Compared with placebo, metreleptin reduced fasting serum insulin concentration, increased adiponectin concentration, reduced the homeostasis model assessment index of insulin resistance, and attenuated postprandial glycemia in response to a mixed meal (all P ≤ .02), but did not affect trunk and peripheral fat mass. HIV control was not affected, and no major adverse effects were observed. Metreleptin administration in HIV-positive, leptin-deficient patients with lipoatrophy treated with pioglitazone improves postprandial glycemia and insulin sensitivity. Results from this pilot study should be confirmed in larger clinical trials.

Trial registration: ClinicalTrials.gov NCT00140244.

Conflict of interest statement

Disclosure statement: There are no conflicts of interest associated with this manuscript

Copyright © 2011 Elsevier Inc. All rights reserved.

Figures

Figure 1

Glucose (top) and insulin (bottom) concentrations and areas-under-the-curve (AUC) in response to a mixed meal before (while symbols) and after (black symbols) 3 months of placebo or metreleptin administration in HIV-infected lipoatrophic men treated with pioglitazone. Compared with placebo, metreleptin significantly attenuated postprandial glycemia (P=0.02 and P=0.01 for the on-treatment and intention-to-treat analyses, respectively), but did not affect postprandial insulinemia (P=0.57 and P=0.82, respectively).