SGLT2 inhibitors and cardiotoxicity in diabetic patients receiving anthracycline therapy: a retrospective study

Abstract Introduction Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are integral in managing heart failure (HF) regardless of ejection fraction or diabetes status. While therapies like ACE inhibitors and beta-blockers are known to protect against chemotherapy-induced cardiotoxicity, evidence for SGLT2i in this context is limited. Purpose To compare the incidence of anthracycline-induced cardiotoxicity in diabetic cancer patients treated with SGLT2i versus other diabetes medications. Methods A retrospective study analyzed 256 cancer patients receiving anthracycline therapy: 136 treated with SGLT2i and 120 with alternative diabetes drugs. Cardiotoxicity was assessed based on heart failure, new cardiomyopathy, arrhythmias, biomarkers (troponin I, NTproBNP), and measures of cardiac function including EF, GLS, RV function, RV strain, and RV-PA coupling. Results Over two years, the SGLT2i group had significantly lower rates of: Heart failure (9.4% vs. 42.8%) HF admissions (3.5% vs. 21.9%) New cardiomyopathy (8.5% vs. 36.4%) Arrhythmias (1.2% vs. 18.4%) Abnormal biomarkers (troponin I: 7.4% vs. 31.7%; NTproBNP: 6.2% vs. 19.2%). Additionally, patients in the SGLT2 group exhibited significantly better preservation of EF (61.4% vs 41.7% p0.05) and global longitudinal strain (GLS) (-18.2% vs. -14.5%, p0.05) compared to the control group. Right ventricular function, assessed by tricuspid annular plane systolic excursion (TAPSE), remained within the normal range in the SGLT2 group (mean TAPSE: 2.3 cm vs. 1.6 cm, p0.05). RV strain, measured via free-wall longitudinal strain (RV-FWLS), was significantly better in the SGLT2 group (-21.5% vs. -17.3%, p0.05). RV-PA coupling, evaluated via the TAPSE/systolic pulmonary artery pressure (sPAP) ratio, was also better preserved in the SGLT2 group, indicating more efficient ventricular-arterial interaction (mean TAPSE/sPAP: 0.38 vs. 0.28, p0.05). Conclusions SGLT2 inhibitors were associated with lower rates of cardiac events, better preservation of left ventricular systolic function, improved GLS, maintained RV function, superior RV-PA coupling, and improved RV strain among patients with cancer and DM treated with anthracyclines. Further studies are warranted to explore the potential cardioprotective effects of SGLT2 inhibitors in high-risk patients receiving cardiotoxic chemotherapy.