Patients with Obesity Caused by Melanocortin-4 Receptor Mutations Can Be Treated with a Glucagon-like Peptide-1 Receptor Agonist

Publication date: Available online 31 May 2018
Source:Cell Metabolism
Author(s): Eva W. Iepsen, Jinyi Zhang, Henrik S. Thomsen, Elizaveta L. Hansen, Mette Hollensted, Sten Madsbad, Torben Hansen, Jens J. Holst, Jens-Christian Holm, Signe S. Torekov
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.

Graphical abstract

Teaser

Iepsen et al. show that the diabetes and obesity drug liraglutide, which has appetite-suppressing effects, caused weight loss in obese patients with mutations in the appetite-regulating melanocortin-4 receptor (MC4R). These results show that the appetite effects of liraglutide are independent of the MC4R pathway and offer therapeutic opportunities for patients with MC4R causal obesity.


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