Glucagon-like peptide-1 receptor agonists are the antidiabetic agents that are associated with the greatest weight loss beyond a marked reduction in glycated haemoglobin. Weight loss results from a reduction in appetite through a predominant central effect combined with a peripheral effect. Liraglutide and semaglutide are developed for the treatment of obesity, independently of type 2 diabetes. Three approaches may be considered to potentiate weight loss: an increase of the drug dosage because of the demonstration of a dose-response, an add-on therapy with a sodium-glucose cotransporter type 2 inhibitor as this agent exerts a complementary action through urinary calorie loss (glucosuria) or a combination of the effects of two incretin hormones (GLP-1 and GIP), as the potent dual agonist tirzepatide currently in development.