Guarding the heart: How SGLT-2 inhibitors protect against chemotherapy-induced cardiotoxicity

• Published in: Current problems in cardiology 2024-03, Vol.49 (3), p.102350, Article 102350
• Main Authors: Vafa, Reza Golchin, Sabahizadeh, Amirreza, Mofarrah, Ramina
• Format: Article
• Language: English
• Subjects: Anthracyclines; Cancer; Cardioprotective agent; Cardiotoxicity; Chemotherapy
• ISSN: 0146-2806; 1535-6280
• DOI: 10.1016/j.cpcardiol.2023.102350

•SGLT-2 inhibitors play an important role in preventing chemotherapy-induced cardiotoxicity.•SGLT-2 inhibitors enhance heart cell viability and reduce cell death.•SGLT-2 inhibitors reduce inflammation by inhibiting reactive oxygen species and inflammatory cytokine production.•SGLT-2 inhibitors enhance the effectiveness of chemotherapy by minimizing potential consequences on the heart. The introduction of chemotherapy agents has significantly transformed cancer treatment, with anthracyclines being one of the most commonly used drugs. While these agents have proven to be highly effective against various types of cancers, they come with complications, including neurotoxicity, nephrotoxicity, and cardiotoxicity. Among these side effects, cardiotoxicity is the leading cause of morbidity and mortality, with anthracyclines being the primary culprit. Chemotherapy medications have various mechanisms that can lead to cardiac injury. Hence, numerous studies have been conducted to decrease the cardiotoxicity of these treatments. Combination therapy with beta-blockers, Angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers have effectively reduced such outcomes. However, a definitive preventive strategy is yet to be established. Meanwhile, sodium-glucose co-transporter-2 (SGLT-2) inhibitors lower blood glucose levels in type 2 diabetes by reducing its re-absorption in the kidneys. They are thus considered potent drugs for glycemic control and reduction of cardiovascular risks. Recent studies have shown that SGLT-2 inhibitors are crucial in preventing chemotherapy-induced cardiotoxicity. They enhance heart cell viability, prevent degenerative changes, stimulate autophagy, and reduce cell death. This drug class also reduces inflammation by inhibiting reactive oxygen species and inflammatory cytokine production. Moreover, it can not only reverse the harmful effects of anticancer agents on the heart structure but also enhance the effectiveness of chemotherapy by minimizing potential consequences on the heart. In conclusion, SGLT-2 inhibitors hold promise as a therapeutic strategy for protecting cancer patients from chemotherapy-induced heart damage and improving cardiovascular outcomes.