Genetic predictors of GLP1 receptor agonist weight loss and side effects

The development of glucagon-like peptide 1 (GLP1) receptor agonists, including semaglutide and tirzepatide, has transformed the clinical management of overweight and obesity. However, substantial inter-person variability exists in both weight loss efficacy and the incidence of side effects1. To investigate the genetic basis of this variability, here we conduct a genome-wide association study of self-reported weight loss and treatment-related side effects in 27,885 people following GLP1 receptor agonist therapy. We identify a missense variant in GLP1R that is associated significantly with increased efficacy of GLP1 medications (P = 2.9 × 10−10), with an additional −0.76 kg of weight loss expected per copy of…

• NI
  National Institutes of Health