SGLT2 inhibitors for prevention and management of cancer treatment-related cardiovascular toxicity: a review of potential mechanisms and clinical insights.

Abstract

More evidence-based strategies are needed for preventing and managing cancer treatment-related cardiovascular toxicity (CTR-CVT). Owing to the growing body of evidence supporting their cardioprotective role in several cardiac injury scenarios, sodium-glucose cotransporter 2 inhibitors (SGLT2i) may be beneficial for preventing and treating CTR-CVT. In October 2024, a search was conducted of the PubMed database to review full studies investigating the cardioprotective role of SGLT2i against CTR-CVT. We identified 44 full published/pre-print studies and 3 ongoing randomised controlled trial across eight types of cancer treatment (anthracyclines, platinum-containing therapy, immune checkpoint inhibitors, HER2-targeted therapies, kinase inhibitors, androgen deprivation therapies, multiple myeloma therapies and 5-fluorouracil). Most studies used animal models and focussed on primary prevention. 43 of the 44 studies found some cardioprotective effect of SGLT2i against CTR-CVT, which in some cases included preventing ejection fraction decline and aberrations in cardiac electrophysiological parameters. Some studies also observed beneficial effects on mortality. A central triad of anti-inflammatory, anti-oxidative and anti-apoptotic mechanisms likely underlie SGLT2i-mediated cardioprotection against CTR-CVT. Overall, this growing body of research suggests that SGLT2i may be a promising candidate for preventing CTR-CVT either as monotherapy or in combination with other cardioprotective drugs. However, the literature is limited in that no prospective randomised controlled trials investigating SGLT2i for the prevention and management of CTR-CVT exist and most existing human retrospective data is based on diabetic populations. Future work must focus on addressing these limitations of the current literature.