Established and Emerging Therapies for Cardiovascular-Kidney-Metabolic Syndrome: Harnessing the Benefits of SGLT-2 Inhibitors, GLP-1 Receptor Agonists, and Beyond

Cardiovascular-kidney-metabolic (CKM) syndrome is a term that is increasingly used to describe interconnected conditions that lead to poor health outcomes, including cardiovascular disease, chronic kidney disease, type 2 diabetes, and obesity. Historically, there have been very few targeted pharmacotherapies available that have changed cardiovascular outcomes for people with CKM syndromes; however, over the past decade, new pharmacologic options have rapidly expanded, with strong evidence for cardiovascular and kidney protective benefits in CKM conditions. Of note, sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists have emerged as key therapeutic options and are now widely guideline-endorsed. However, amid a growing pipeline of therapeutic classes on the horizon, real-world use of these agents has become increasingly complex. This review will compare the efficacy of these therapies, exploring their distinct and complementary mechanisms, with consideration to their role in contemporary clinical care. Emerging classes of therapy that may confer additional benefits for people with CKM syndrome will also be highlighted.