title: Efficacy and Safety of Metreleptin in Patients with Partial Lipodystrophy: Lessons from an Expanded Access Program.
abstract: OBJECTIVE
  Patients with lipodystrophy have severe metabolic abnormalities (insulin resistance, diabetes, and hypertriglyceridemia) that may increase morbidity and mortality. Metreleptin is approved by the United States Food and Drug Administration for treatment of generalized forms of lipodystrophy. We aimed to determine the efficacy and safety of metreleptin among patients with partial lipodystrophy using an expanded-access model.
  
  
  METHODS
  Study FHA101 (ClinicalTrials.gov identifier: NCT00677313) was an open-label, expanded-access, long-term clinical effectiveness and safety study in 23 patients with partial lipodystrophy and diabetes and/or hypertriglyceridemia with no prespecified leptin level. Metreleptin was administered subcutaneously at 0.02 mg/kg twice daily (BID) at Week 1, followed by 0.04 mg/kg BID at Week 2. Dose adjustments thereafter were based on patient response (maximum dose of 0.08 mg/kg BID). One-year changes in glycated hemoglobin (HbA1c), fasting plasma glucose, triglycerides, alanine and aspartate aminotransferases, and treatment-emergent adverse events (TEAEs) were evaluated.
  
  
  RESULTS
  HbA1c, fasting plasma glucose, and triglycerides were numerically decreased throughout 1 year, with mean (standard error) changes from baseline of -0.88 (0.62)%, -42.0 (22.4) mg/dL, and -119.8 (84.1) mg/dL, respectively, which were greater among patients with higher baseline abnormalities. Liver enzymes did not worsen, and the most frequently observed TEAEs (≥ 10% incidence) were mild to moderate and included nausea (39.1%), hypoglycemia (26.1%), and urinary tract infections (26.1%)-all reported previously. There were no reports of clinically significant immune-related adverse events or new safety signals.
  
  
  CONCLUSIONS
  Our clinical observations document the large heterogeneity and disease burden of partial lipodystrophy syndromes and suggest that metreleptin treatment benefits may extend to patients with partial lipodystrophy. Additional studies are needed to confirm these preliminary findings.
authors.affiliation: Brehm Center for Diabetes Research and Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Nevin
authors.initials: N
authors.lastname: Ajluni
authors.affiliation: Greenville Veterans Affairs Health Care Center, Division of Endocrinology and Metabolism, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
authors.forename: Moahad
authors.initials: M
authors.lastname: Dar
authors.affiliation: AstraZeneca, Gaithersburg, MD, USA.
authors.forename: John
authors.initials: J
authors.lastname: Xu
authors.affiliation: Brehm Center for Diabetes Research and Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Adam H
authors.initials: AH
authors.lastname: Neidert
authors.affiliation: Brehm Center for Diabetes Research and Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Elif A
authors.initials: EA
authors.lastname: Oral
keywords: Diabetes; Hypertriglyceridemia; Metreleptin; Partial lipodystrophy