In people living with type 2 diabetes inadequately managed with GLP-1 RA therapy, with or without additional oral glucose-lowering medications, switching to once-weekly IcoSema, compared with once-weekly semaglutide 1.0 mg, demonstrated statistical superiority in HbA1c reduction, similar rates of clinically significant or severe hypoglycaemic episodes and comparable gastrointestinal tolerability. The gene discussed is GLP1R; the disease is type 2 diabetes mellitus.