Expanding the scope of SGLT inhibitors in underrepresented cardiac populations: from pathophysiology to clinical evidence
Abstract
Sodium-glucose cotransporter inhibitors, originally developed for diabetes management, have demonstrated significant therapeutic benefit across the phenotypic spectrum of heart failure in landmark trials. However, multiple patient populations predisposed to ventricular dysfunction, including transthyretin amyloid cardiomyopathy, hypertrophic cardiomyopathy, congenital heart disease, heart transplant, and left ventricular assist devices, were initially excluded from these key trials due to their unique underlying cardiac physiology and limited safety data. Nonetheless, the pleiotropic effects of SGLTi, like modulation of inflammation, fibrosis, systemic venous congestion, endothelial dysfunction, and renal impairment, may also be advantageous in these patient populations. This narrative review discusses the potential role of SGLTi in these populations, primarily based on current observational evidence. We also examine emerging mechanistic insights from preclinical research and summarize ongoing clinical trials that may further clarify the therapeutic potential of SGLTi in these contexts. Finally, safety considerations, including monitoring volume status, the risk of euglycemic ketoacidosis, and genitourinary infections, are discussed. Ongoing prospective studies and interventional trials will be essential to better define the safety and efficacy of SGLTi in these underrepresented patient groups.
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