Cardiovascular outcome trials (CVOTs) in cardiorenal metabolic medicine: a decade of transformative progress (2016–2026)

The decade from 2016 to 2026 has witnessed an extraordinary transformation in cardiometabolic medicine, propelled by the maturation of cardiovascular outcome trials (CVOTs). What began as regulatory requirements to establish cardiovascular safety for novel glucose-lowering agents has evolved into a robust body of evidence demonstrating profound cardiorenal protective effects-often extending beyond diabetes itself. Landmark trials such as EMPA-REG OUTCOME, LEADER, SELECT, SURPASS-CVOT, and VESALIUS-CV have not only redefined therapeutic priorities but have also catalyzed a conceptual shift from glucocentric management to an integrated cardiorenal metabolic (CRM) framework. This narrative review traces the epidemiological imperatives driving this evolution, chronicles the historical trajectory of CVOTs, synthesizes key findings across major pharmacological classes, and reflects on emerging therapies and risk markers that are shaping the precision-medicine paradigm of 2026.