The development of glucagon-like peptide 1 receptor (GLP-1R) agonists, such as semaglutide and tirzepatide, has been a game changer in the clinical management of overweight and obesity, but there is interpersonal variability in efficacy of these medications for weight loss, as well as in the incidence of undesired side effects. Investigators from the 23andMe Research Institute have shed some light on how variations in the GLP-1R and GIP receptor (GIPR) genes impact their effectiveness and the occurrence of side effects.