title: Clinical effects of long-term metreleptin treatment in patients with lipodystrophy.
abstract: OBJECTIVE
  To evaluate the long-term clinical effect of treatment with metreleptin (an analogue of human leptin) on glycemic and lipid abnormalities and markers of hepatic steatosis in patients with inherited or acquired lipodystrophy.
  
  
  METHODS
  Fifty-five patients (36 with generalized lipodystrophy and 19 with partial lipodystrophy) with at least 1 of 3 metabolic abnormalities (diabetes mellitus, fasting triglyceride level ≥200 mg/dL, and insulin resistance) and low leptin levels received subcutaneous injections of metreleptin once or twice daily in an ongoing clinical trial at the National Institutes of Health.
  
  
  RESULTS
  At baseline, hemoglobin A1c-8.5% ± 2.1% (mean ± standard deviation [SD])-and triglycerides-479 ± 80 mg/dL (geometric mean ± standard error [SE])-were substantially elevated. Robust and sustained reductions in both variables were evident for the observed patient population during a 3-year metreleptin treatment period (-2.1% ± 0.5% [mean ± SE] and -35.4% ± 13.7% [mean ± SE], respectively). Mean alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were elevated at baseline (100 ± 120 U/L and 71 ± 77 U/L [mean ± SD], respectively) and decreased by -45 ± 19 U/L and -33 ± 14 U/L (mean ± SE), respectively, during the 3-year metreleptin treatment period. Improvements in hemoglobin A1c, triglycerides, ALT, and AST were more pronounced in the subsets of patients having elevated levels at baseline. The most notable adverse events observed in this patient population were likely attributable to underlying metabolic abnormalities or comorbidities.
  
  
  CONCLUSIONS
  Metreleptin treatment substantially reduced glycemic variables, triglycerides, and liver enzymes (ALT and AST) and demonstrated durability of response throughout a 3-year treatment period. These results support metreleptin as a potential treatment for certain metabolic disorders (for example, diabetes mellitus and hypertriglyceridemia) associated with lipodystrophy.
authors: Amylin Pharmaceuticals, Inc., San Diego, California 92121, USA. Jean.Chan@amylin.com
authors: Jean L
authors: JL
authors: Chan
authors: Karen
authors: K
authors: Lutz
authors: Elaine
authors: E
authors: Cochran
authors: Wenying
authors: W
authors: Huang
authors: Yvette
authors: Y
authors: Peters
authors: Christian
authors: C
authors: Weyer
authors: Phillip
authors: P
authors: Gorden
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002648:Child; D015331:Cohort Studies; D005234:Fatty Liver / Q000209:etiology / Q000517:prevention & control; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D015228:Hypertriglyceridemia / Q000209:etiology / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D020738:Leptin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008060:Lipodystrophy / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008099:Liver / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D020738:Leptin; C517652:hemoglobin A1c protein, human; C415771:metreleptin