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Cited by 65Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesGrowth Hormone and Insulin-like Growth Factors

Effects of Metreleptin in Pediatric Patients With Lipodystrophy

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Brown, Rebecca J., Meehan, Cristina Adelia, Cochran, Elaine, Rother, Kristina I., Kleiner, David E., Walter, Mary, Gorden, Phillip·2017·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2016-3628PMC PMC5443330
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Abstract

Context: Lipodystrophy syndromes are rare disorders of deficient adipose tissue. Metreleptin, a human analog of leptin, improved metabolic abnormalities in mixed cohorts of children and adults with lipodystrophy and low leptin. Objective: Determine effects of metreleptin on diabetes, hyperlipidemia, nonalcoholic fatty liver disease (NAFLD), growth, and puberty in pediatric patients with lipodystrophy and low leptin. Design: Prospective, single-arm, open-label studies with continuous enrollment since 2000. Setting: National Institutes of Health, Bethesda, Maryland. Patients: Fifty-three patients aged 6 months to <18 years with lipodystrophy, leptin level <8 ng/mL (male patients) or <12 ng/mL (female patients), and ≥1 metabolic abnormality (diabetes, insulin resistance, or hypertriglyceridemia). Intervention: Subcutaneous metreleptin injections (0.04 to 0.19 mg/kg/d). Main Outcome Measures: Change in A1c, lipid, and transaminase levels after a mean ± standard deviation (SD) of 12 ± 0.2 months and 61 ± 39 months. Changes in liver histology, growth, and pubertal development throughout treatment. Results: After 12 months, the A1c level (mean ± SD) decreased from 8.3% ± 2.4% to 6.5% ± 1.8%, and median triglyceride level decreased from 374 mg/dL [geometric mean (25th,75th percentile), 190, 1065] to 189 mg/dL (112, 334; P < 0.0001), despite decreased glucose- and lipid-lowering medications. The median [geometric mean (25th,75th percentile)] alanine aminotransferase level decreased from 73 U/L (45, 126) to 41 U/L (25, 59; P = 0.001), and that of aspartate aminotransferase decreased from 51 U/L (29, 90) to 26 U/L (18, 42; P = 0.0002). These improvements were maintained over long-term treatment. In 17 patients who underwent paired biopsies, the NAFLD activity score (mean ± SD) decreased from 4.5 ± 2.0 to 3.4 ± 2.0 after 3.3 ± 3.2 years of metreleptin therapy (P = 0.03). There were no clinically significant changes in growth or puberty. Conclusion: Metreleptin lowered A1c and triglyceride levels, and improved biomarkers of NAFLD in pediatric patients with lipodystrophy. These improvements are likely to reduce the lifetime burden of disease.

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  • Human studies including children demonstrated that metreleptin improves hyperglycemia, hypertriglyceridemia, and hepatic fatty steatosis in patients with lipodystrophy characterized by congenital or acquired loss of adipose tissue.

    “Human studies including children have demonstrated the effect of Metreleptin on improving hyperglycemia, hypertriglyceridemia, and hepatic fatty steatosis in patients with lipodystropy characterized by congenital or acquired loss of adipose tissue [84, 85].”

    From Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand? (2021) · cites this paper as [85]

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Research works printed but not linked: 2

  1. Greulich W, Pyle S. Radiographic Atlas of Skeletal Development of the Hand and Wrist. 2nd ed. Stanford, CA: Stanford University Press; 1959.
  2. N Engl J Med. 1975;292(1):35-41.

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Authors
Brown, R. J., Meehan, C. A., Cochran, E., Rother, K. I., Kleiner, D. E., Walter, M., & Gorden, P.
Affiliations
National Institutes of Health (US)
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2017-01-23
Volume
102
Issue
5
Pages
1511-1519
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2016-3628
PMC
PMC5443330
OpenAlex
W2611388722
Cited by
65
References
32
Citations by year
2026: 5 · 2025: 9 · 2024: 6 · 2023: 6 · 2022: 8 · 2021: 11 · 2020: 3 · 2019: 10 · 2018: 6 · 2017: 1
FWCI
3.35
Type
journal article
Language
en
Open access
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Amgen
  • Bristol-Myers Squibb
  • Amylin Pharmaceuticals
  • National Institutes of Health
  • National Cancer Institute (20892)
  • National Institute of Diabetes and Digestive and Kidney Diseases
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords
metreleptin, lipodystrophy, pediatric patients, leptin deficiency, diabetes mellitus, hypertriglyceridemia, insulin resistance, non-alcoholic fatty liver disease, liver enzymes, growth, puberty, adipose tissue deficiency, statins, fibrates, lipid-lowering therapy, HbA1c, transaminases
MeSH terms
Adolescent, Alanine Transaminase, Hypolipidemic Agents, Aspartate Aminotransferases, Blood Glucose, Body Height, Child, Child, Preschool, Diabetes Mellitus, Type 2, Female, Glycated Hemoglobin, Humans, Hyperlipidemias, Hypoglycemic Agents, Infant, Insulin Resistance, Lipodystrophy, Liver, Male, Prospective Studies, Puberty, Triglycerides, Cohort Studies, Leptin, Non-alcoholic Fatty Liver Disease

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