Type 2 diabetes mellitus (T2D) represents a significant public health problem, with a dramatically increasing prevalence. T2D is considered a progressive disease that develops macro- and microvascular complications such as cardiovascular disease (CVD), heart failure (HF), and chronic kidney disease (CKD), which are closely interconnected and constitute the main causes of morbidity and mortality in these patients. Over time, finding new pharmacological approaches to protect against these cardiorenal events (the “cardiorenal continuum”) has become the fundamental objective of research aimed at these patients.
Until a few years ago, treatment guidelines recommended a glucocentric approach to T2D, but the appearance of new therapeutic agents such as sodium-glucose cotransporter 2 inhibitors (SGLT2i) or glucagon-like peptide 1 receptor agonists (GLP-1 RA) has meant a radical change evolving to a more holistic approach in which the cardiac and renal protection of patients plays a paramount role in addition to glycemic/metabolic control .
SGLT2i are a modern drug class of glucose-lowering agents, with a particular mechanism of action independent of β‐cell function and insulin secretion, whose use in patients with T2D has increased in the past few years. By inhibiting the SGLT2 receptor, these drugs increase glycosuria and natriuresis, promoting different metabolic benefits and limiting the risk of hypoglycemia in patients with diabetes . Also, these drugs demonstrate the potential to be used at any stage of T2D, alone or in combination with any class of glucose‐lowering agent. Moreover, these agents have been proven to exert direct nephroprotective and cardioprotective effects  with important effects beyond their glucose-regulating role.
These benefits have led to the study of SGLT2i in patients with different cardiorenal disease phenotypes. Evidence from EMPA-REG OUTCOME, CANVAS Program, DECLARE-TIMI 58, VERTIS-CV, CREDENCE, and more recently DAPA-HF, EMPEROR-Reduced, EMPEROR-Preserved, and DAPA-CKD show that the beneficial effects of SGLT2i are observed across all stages of the cardiorenal continuum, ranging from patients with diabetes and multiple risk factors to those with established cardiovascular/renal disease and even independently of T2D status [4, 5].
The benefits observed in these clinical trials have been confirmed in real-life studies in which SGLT2i have been associated with significantly lower risks of all-cause mortality, hospitalization for HF, and major kidney events compared with other glucose-lowering drugs. In addition, this current understanding of the pathophysiological pathways of SGLT2i places this class of drugs in an individualized patient-centered approach and allows clinicians to intervene in different stages of the cardiorenal continuum.
This supplement summarizes all the evidence of this therapeutic change and reviews the role of these drugs from prevention to management of patients who have already developed complications, such as patients with HF and chronic kidney disease.