1. Patients with Obesity Caused by Melanocortin-4 Receptor Mutations Can Be Treated with a Glucagon-like Peptide-1 Receptor Agonist.
- Author
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Iepsen EW, Zhang J, Thomsen HS, Hansen EL, Hollensted M, Madsbad S, Hansen T, Holst JJ, Holm JC, and Torekov SS
- Subjects
- Adult, Appetite drug effects, Female, Humans, Hypoglycemic Agents pharmacology, Liraglutide pharmacology, Male, Middle Aged, Mutation, Weight Loss drug effects, Glucagon-Like Peptide-1 Receptor antagonists & inhibitors, Hypoglycemic Agents therapeutic use, Liraglutide therapeutic use, Obesity drug therapy, Obesity genetics, Receptor, Melanocortin, Type 4 genetics
- Abstract
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., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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