Metreleptin and generalized lipodystrophy and evolving therapeutic perspectives

Tchang, Beverly G; Shukla, Alpana P; Aronne, Louis J

doi:10.1517/14712598.2015.1052789

Cited by 28Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesPharmacology and Obesity Treatment

Metreleptin and generalized lipodystrophy and evolving therapeutic perspectives

Tchang, Beverly G, Shukla, Alpana P, Aronne, Louis J·2015·Expert Opinion on Biological Therapy

DOI 10.1517/14712598.2015.1052789

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Abstract

INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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.

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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 [84]

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Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand?
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Authors: Tchang, B. G., Shukla, A. P., & Aronne, L. J.
Affiliations: Weill Cornell Medicine (US)
ORCID: Tchang, Beverly G
Shukla, Alpana P
Aronne, Louis J
Venue: Expert Opinion on Biological Therapy
Publisher: Informa Healthcare
Published: 2015-06-10
Volume: 15
Issue: 7
Pages: 1061-1075
ISSN: 1471-2598 (ISSN-L)
1744-7682
DOI: 10.1517/14712598.2015.1052789
OpenAlex: W1790185087
Cited by: 28
References: 94
Citations by year: 2026: 1 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 5 · 2016: 3 · 2015: 1 · 2012: 1
FWCI: 0.44
Type: journal article
Language: en
Open access: closed
Locations: Expert Opinion on Biological Therapy (publishedVersion)
PubMed (publishedVersion)
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 › Pharmacology › Pharmacology and Obesity Treatment
Keywords: metreleptin, recombinant human leptin, generalized lipodystrophy, leptin deficiency, familial partial lipodystrophy, HIV-associated lipodystrophy, non-alcoholic fatty liver disease, obesity, hormone replacement therapy, immunogenicity, drug safety
MeSH terms: Clinical Trials as Topic, Half-Life, Humans, Lipodystrophy, Obesity, Signal Transduction, Autoimmunity, Leptin, Lipodystrophy, Congenital Generalized

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Metreleptin and generalized lipodystrophy and evolving therapeutic perspectives

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