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Patients with Obesity Caused by Melanocortin-4 Receptor Mutations Can Be Treated with a Glucagon-like Peptide-1 Receptor Agonist
Open accessAbstract
Pathogenic mutations in the appetite-regulating melanocortin-4 receptor (MC4R) represent the most common cause of monogenic obesity with limited treatment options. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) cause weight loss by reducing appetite. We assessed the effect of the GLP-1 RA liraglutide 3.0 mg for 16 weeks in 14 obese individuals with pathogenic MC4R mutations (BMI 37.5 ± 6.8) and 28 matched control participants without MC4R mutation (BMI 36.8 ± 4.8). Liraglutide decreased body weight by 6.8 kg ± 1.8 kg in individuals with pathogenic MC4R mutations and by 6.1 kg ± 1.2 kg in control participants. Total body fat, waist circumference, and fasting and postprandial glucose concentrations similarly decreased in both groups. Thus, liraglutide induced an equal, clinically significant weight loss of 6% in both groups, indicating that the appetite-reducing effect of liraglutide is preserved in MC4R causal obesity and that liraglutide acts independently of the MC4R pathway. Thus, liraglutide could be an effective treatment of the most common form of monogenic obesity.
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“Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is used in the treatment of obesity because it induces weight loss 21-23 and maintains low-calorie diet-induced weight loss for at least 1 year, 11,24 primarily by means of appetite inhibition. 25”
From Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined (2021) · cites this paper as [23]
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“Short-term studies have demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RA) induce weight loss by promoting satiety and reducing hunger16–19.”
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“there is evidence from a small clinical study with liraglutide20 that they may be effective in people with MC4R deficiency.”
From Tirzepatide leads to weight reduction in people with obesity due to MC4R deficiency (2025) · cites this paper as [20]
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“ment with liraglutide has been shown to benefit patients with obesity caused by MC4R mutations.(64,65) However, liraglutide has not been approved for this indication.”
BackgroundThe promise of new anti-obesity therapies arising from knowledge of genetic obesity traits
Hinney, A., Körner, A., & Fischer-Posovszky, P. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00716-0 · Cited by 101
Metadata
- Authors
- Iepsen, E. W., Zhang, J., Thomsen, H. S., Hansen, E. L., Hollensted, M., Madsbad, S., Hansen, T., Holst, J. J., Holm, J.-C., & Torekov, S. S.
- Affiliations
- University of Copenhagen (DK)
- Herlev Hospital (DK)
- Hvidovre Hospital (DK)
- Holbæk Sygehus (DK)
- Corresponding author
- Iepsen, Eva W.
- Torekov, Signe S.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 28
- Issue
- 1
- Pages
- 23-32.e3
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2806545464
- Cited by
- 156
- References
- 59
- Citations by year
- 2026: 18 · 2025: 15 · 2024: 25 · 2023: 24 · 2022: 22 · 2021: 21 · 2020: 22 · 2019: 6 · 2018: 3
- FWCI
- 7.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Lundbeckfonden
- Region Sjælland
- Danish Diabetes Academy
- Novo Nordisk Fonden
- Aase og Ejnar Danielsens Fond (NNF15CC0018486)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Pharmacology (medical) › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- melanocortin-4 receptor, MC4R mutations, monogenic obesity, liraglutide, GLP-1 receptor agonists, weight loss, appetite regulation, fat mass, fasting and postprandial glucose, obesity treatment
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Liraglutide, Adult, Appetite, Female, Humans, Hypoglycemic Agents, Male, Middle Aged, Mutation, Obesity, Weight Loss, Receptor, Melanocortin, Type 4
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