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Clinical Effects of Long-Term Metreleptin Treatment in Patients with Lipodystrophy.
MedLine Citation:
PMID:  22068254     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE - Treatment with an analog of human leptin, metreleptin, has been shown to benefit the metabolic abnormalities in patients with rare syndromes of inherited or acquired lipodystrophy. The objective of this analysis was to evaluate the long-term clinical effect of metreleptin on glycemic and lipid abnormalities and markers of hepatic steatosis in patients with lipodystrophy.METHODS - Fifty-five patients (36 generalized lipodystrophy, 19 partial lipodystrophy) with at least 1 of 3 metabolic abnormalities (diabetes mellitus, fasting triglycerides ≥200mg/dL, and/or 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 - HbA1c (8.5±2.1% [mean ± SD]) and triglycerides (479±80 mg/dL, [geometric mean ± SE]) were markedly elevated at baseline. Robust and sustained reductions in both parameters were evident for the observed population over a 3-year treatment period (-2.1±0.5% [mean ± SE] and -35.4±13.7% [mean ± SE], respectively). Mean alanine transaminase (ALT) and aspartate transaminase (AST) levels were elevated at baseline (100±120 and 71±77 U/L [mean ± SD], respectively) and decreased by -45±19 U/L and -33±14 U/L (mean ± SE), respectively, over the 3-year treatment period. Improvements in HbA1c, 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 population were likely attributed to underlying metabolic abnormalities or co-morbidities.CONCLUSIONS - Metreleptin treatment substantially reduced glycemic parameters, triglycerides, and liver enzymes, and demonstrated durability of response over a 3-year treatment period. These results support metreleptin as a potential treatment for certain metabolic disorders (e.g., diabetes mellitus and/or hypertriglyceridemia) associated with lipodystrophy.
Authors:
Jean L Chan; Karen Lutz; Elaine Cochran; Wenying Huang; Yvette Peters; Christian Weyer; Phillip Gorden
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-8
Journal Detail:
Title:  Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists     Volume:  -     ISSN:  1934-2403     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9607439     Medline TA:  Endocr Pract     Country:  -    
Other Details:
Languages:  ENG     Pagination:  1-31     Citation Subset:  -    
Affiliation:
Amylin Pharmaceuticals, San Diego, CA.
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