title: Metreleptin and generalized lipodystrophy and evolving therapeutic perspectives.
abstract: BACKGROUND
  Metreleptin was recently approved by the Food and Drug Administration for the treatment of generalized lipodystrophy, a condition characterized by leptin deficiency. Its efficacy as hormone replacement therapy suggests broader applications in diseases also characterized by leptin abnormalities, such as familial partial lipodystrophy (FPLD), non-alcoholic fatty liver disease (NAFLD), and common obesity. Metreleptin, in conjunction with other pharmacologic interventions, has the potential to address one of the most widespread epidemics of our time, obesity.
  
  
  METHODS
  This review covers the physiology of leptin, the pharmacologic properties of recombinant methionyl human leptin (R-metHu-Leptin, metreleptin), evidence for metreleptin's efficacy in the treatment of generalized lipodystrophy from both completed and ongoing clinical trials, safety concerns, and future directions in metreleptin research.
  
  
  CONCLUSIONS
  Metreleptin's approval for generalized lipodystrophy is the first step in defining and expanding its role to other metabolic diseases. Clinical trials are underway to delineate its efficacy in FPLD, human immunodeficiency virus/highly active anti-retroviral therapy-associated acquired lipodystrophy (HAL), and NAFLD. Additionally, there is growing data that support a therapeutic role in obesity. One of the barriers to development, however, is metreleptin's safety and immunogenicity. Further advances in biologic compatibility are required before metreleptin can be approved for additional indications.
authors.affiliation: Weill Cornell Medical College, Comprehensive Weight Control Center, Division of Endocrinology, Diabetes & Metabolism , 1165 York Avenue, New York, NY, 10065 , USA ljaronne@med.cornell.edu.
authors.forename: Beverly G
authors.initials: BG
authors.lastname: Tchang
authors.forename: Alpana P
authors.initials: AP
authors.lastname: Shukla
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Aronne
mesh_terms: D015551:Autoimmunity; D002986:Clinical Trials as Topic; D006207:Half-Life; D006801:Humans; D020738:Leptin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D008060:Lipodystrophy / Q000145:classification / Q000188:drug therapy / Q000209:etiology; D052497:Lipodystrophy, Congenital Generalized / Q000145:classification / Q000188:drug therapy* / Q000209:etiology; D009765:Obesity / Q000188:drug therapy; D015398:Signal Transduction
chemical_list: D020738:Leptin; C122136:recombinant methionyl human leptin; C415771:metreleptin
keywords: leptin; lipodystrophy; metreleptin; obesity; r-metHu-Leptin