The recent availability of once-weekly subcutaneous 2.4 mg semaglutide (a glucagon-like peptide-1 receptor agonist; WegovyTM Novo Nordisk A/S, Bagsværd, Denmark) has changed the scene, and semaglutide is considered a ‘game changer’ in the treatment of obesity. The gene discussed is GLP1R; the disease is obesity due to melanocortin 4 receptor deficiency.