Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist
Abstract
Patients with rare defects in the gene encoding proopiomelanocortin (POMC) have extreme early-onset obesity, hyperphagia, hypopigmentation, and hypocortisolism, resulting from the lack of the proopiomelanocortin-derived peptides melanocyte-stimulating hormone and corticotropin. In such patients, adrenal insufficiency must be treated with hydrocortisone early in life. No effective pharmacologic treatments have been available for the hyperphagia and obesity that characterize the condition. In this investigator-initiated, open-label study, two patients with proopiomelanocortin deficiency were treated with setmelanotide, a new melanocortin-4 receptor agonist. The patients had a sustainable reduction in hunger and substantial weight loss (51.0 kg after 42 weeks in Patient 1 and 20.5 kg after 12 weeks in Patient 2).
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The large weight loss caused by setmelanotide did not appear to promote substantial reductions in blood pressure that would normally be expected with such large decreases in body weight and fat mass.
“However, the large weight loss caused by setmelanotide did not appear to promote substantial reductions in BP that would normally be expected with such large decreases in body weight and fat mass.”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [79]
In two patients with POMC deficiency, setmelanotide treatment produced sustained reduction in hunger.
“In a recent open-label study, two patients with POMC deficiency were treated with setmelanotide and experienced sustained reduction in hunger and substantial weight loss (51.0 kg after 42 weeks in one patient and 20.5 kg after 12 weeks in the second patient) without significant increases in BP or HR [79].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [79]
In two patients with POMC deficiency, setmelanotide treatment produced substantial weight loss.
“In a recent open-label study, two patients with POMC deficiency were treated with setmelanotide and experienced sustained reduction in hunger and substantial weight loss (51.0 kg after 42 weeks in one patient and 20.5 kg after 12 weeks in the second patient) without significant increases in BP or HR [79].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [79]
In two patients with POMC deficiency, setmelanotide treatment produced no significant increases in blood pressure or heart rate.
“In a recent open-label study, two patients with POMC deficiency were treated with setmelanotide and experienced sustained reduction in hunger and substantial weight loss (51.0 kg after 42 weeks in one patient and 20.5 kg after 12 weeks in the second patient) without significant increases in BP or HR [79].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [79]
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“Setmelanotide showed excellent outcomes in two patients with pro-opiomelanocortin (POMC) deficiency, reversing hyperphagia and producing dramatic weight loss in both patients.(4) When given to three patients with leptin receptor (LEPR) deficiency, setmelanotide produced clinically significant reduction in both body we…”
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- Authors
- Kühnen, P., Clément, K., Wiegand, S., Blankenstein, O., Gottesdiener, K., Martini, L. L., Mai, K., Blume-Peytavi, U., Grüters, A., & Krude, H.
- Affiliations
- Inserm (FR)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2016-07-21
- Volume
- 375
- Issue
- 3
- Pages
- 240-246
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2503348180
- Cited by
- 485
- References
- 18
- Citations by year
- 2026: 32 · 2025: 23 · 2024: 52 · 2023: 61 · 2022: 41 · 2021: 65 · 2020: 53 · 2019: 41 · 2018: 56 · 2017: 52 · 2016: 7 · 2013: 1
- FWCI
- 33.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- setmelanotide, melanocortin-4 receptor agonist, early-onset obesity, hyperphagia, hypothalamic obesity, appetite suppression, weight loss, adrenal insufficiency, cortisol, melanocyte-stimulating hormone, ACTH, rare genetic disorders
- MeSH terms
- Adult, alpha-MSH, Blood Pressure, Female, Humans, Hyperphagia, Metabolism, Inborn Errors, Obesity, Phenotype, Pilot Projects, Pro-Opiomelanocortin, Receptor, Melanocortin, Type 4, Young Adult
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