Managing glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors in clinical practice

The obesity epidemic has significantly heightened the impact of cardiometabolic risk factors on the global burden of cardiovascular and kidney diseases. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is), originally developed for type 2 diabetes treatment, have demonstrated in randomised controlled trials their ability to reduce the risk of cardiovascular and kidney diseases. This has led to substantial improvements in patient outcomes. SGLT2i, in particular, are the first class of drugs proven to improve the prognosis of patients with heart failure with preserved ejection fraction, and evidence is accumulating to suggest that also GLP-1RA might be beneficial in these patients. Remarkably, the benefits of GLP-1RA and SGLT2i are independent of type 2 diabetes status or baseline renal function. The critical role of these drug classes in managing high cardiovascular risk patients is increasingly acknowledged in guidelines, which now advocate their use across broader clinical phenotypes. This review compiles evidence supporting the use of these drugs in various clinical scenarios, highlighting their impact on outcomes and identifying patient subgroups most likely to benefit from their prescription. Guideline recommendations are summarised at the conclusion of each section. In the conclusion, we highlight how these drugs have changed our approach to cardiometabolic diseases and emphasise the potential advantages achievable by using their reciprocal combination and combinations with other drugs representing the foundation of the guidelines-directed medical therapy.