title: 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.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. fmagkos@bidmc.harvard.edu
authors.forename: Faidon
authors.initials: F
authors.lastname: Magkos
authors.forename: Aoife
authors.initials: A
authors.lastname: Brennan
authors.forename: Laura
authors.initials: L
authors.lastname: Sweeney
authors.forename: Eun Seok
authors.initials: ES
authors.lastname: Kang
authors.forename: John
authors.initials: J
authors.lastname: Doweiko
authors.forename: Adolf W
authors.initials: AW
authors.lastname: Karchmer
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D052242:Adiponectin / Q000097:blood; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D001786:Blood Glucose; D015992:Body Mass Index; D004359:Drug Therapy, Combination; D015497:HIV-1; D039682:HIV-Associated Lipodystrophy Syndrome / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D000077205:Pioglitazone; D019518:Postprandial Period / Q000187:drug effects*; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D045162:Thiazolidinediones; C415771:metreleptin; D000077205:Pioglitazone