Glucagon-like receptor 1 (GLP-1) receptor agonists have been shown to have cardiorenal benefits in overweight and obese individuals with and without type 2 diabetes. Following the discovery of exendin-4 and the development of exenatide, a number of studies have been published demonstrating benefits of this class of agents beyond improvements in glycaemic control. In obese non-diabetic humans with established cardiovascular disease, semaglutide reduced the risk of cardiovascular end point (composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in a time-to-first-event analysis), independent of baseline adiposity and irrespective of whether or not subjects lost weight or improved glycaemia. Even greater weight loss is observed in studies of GLP-1/gastric inhibitory polypeptide (GIP) receptor ‘twincretin’ agonists (e.g. tirzepatide), GLP-1/glucagon receptor coagonists (e.g. survodutide, mazdutide) and GLP-1/GIP/glucagon receptor triple agonists (e.g. retatrutide). A number of trials are underway examining the potential cardiometabolic benefits of semaglutide in individuals with type 1 diabetes, aimed at reducing postprandial hyperglucagonaemia and insulin-induced weight gain. Finally, benefits of GLP-1 receptor agonists in relation to dementia, Parkinson’s disease and other non-metabolic conditions may expand the use of these agents in the future. Major challenges, such as how to minimise loss of lean mass with these agents, and the most cost-effective way to ensure equitable access to these drugs, are still to be addressed.