GLP-1 Receptor Agonist Treatment in Morbid Obesity and Type 2 Diabetes Due to Pathogenic Homozygous Melanocortin-4 Receptor Mutation: A Case Report

Individuals with obesity due to pathogenic heterozygous melanocortin 4 receptor (MC4R) mutations can be treated efficiently with the glucagon-like peptide-1 receptor agonist (GLP-1 RA) liraglutide. Here, we report the effect of 16 weeks of liraglutide 3 mg/day treatment in a woman with morbid obesity and type 2 diabetes (T2D) due to homozygous pathogenic MC4R mutation. The body weight loss was 9.7 kg, similar to weight loss in heterozygous MC4R mutation carriers and common obesity. In addition, the treatment led to clinically relevant decreases in fasting glucose, triglycerides, systolic blood pressure, and normalization of glucose tolerance. We conclude that liraglutide reduces body weight and blood glucose levels in hetero- and homozygous MC4R mutation carriers. This serves as proof-of-concept that MC4Rs are not required for the body weight and glucose lowering effects of GLP-1 RAs and that liraglutide may be used as part of the treatment of obesity and T2D due to MC4R mutations. [Display omitted] Liraglutide induces weight loss in a woman homozygous for pathogenic MC4R mutationGlucose tolerance normalized and fasting glucose and triglyceride levels reducedMC4R is not required for GLP-1 RA-mediated weight lossLiraglutide is an effective treatment for the most common form of monogenic obesity In this case report, Iepsen et al. show that the GLP-1 RA liraglutide induces a weight loss of 10 kg and normalization of glucose tolerance in a woman homozygous for pathogenic MC4R mutation. Thus, the appetite-reducing effects of liraglutide are preserved in MC4R causal obesity and independent of the MC4R pathway.