Tirzepatide leads to weight reduction in people with obesity due to MC4R deficiency.

ABSTRACT: The magnitude of weight reduction in the SURMOUNT-1 trial of the dual GLP-1 and GIP receptor agonist tirzepatide suggests that this treatment may be particularly effective in addressing the treatment needs of people with severe obesity (body mass index >40 kg m^-2), some of whom may carry rare penetrant genetic variants. Here we investigated the clinical response of men and women in the SURMOUNT-1 trial who carried pathogenic mutations in the melanocortin 4 receptor (MC4R) gene, the most common genetic cause of obesity. We found that 32 of 2,291 people (1.4%) for whom data were available carried pathogenic MC4R mutations. At baseline, MC4R mutation carriers exhibited a higher body mass index compared with noncarriers (40 kg m^-2 versus 38 kg m^-2; P = 0.036).

SUBMITTER: Bhatnagar P 

PROVIDER: S-EPMC12532586 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature