Association between SGLT2 inhibitor use and heart failure outcomes in anthracycline-exposed patients: a meta-analysis

Background Anthracyclines are among the chemotherapeutic agents most strongly associated with cancer therapy–related cardiac dysfunction (CTRCD) and represent the class with the highest incidence of cardiotoxicity, affecting up to one third of exposed patients. Anthracycline-induced cardiotoxicity frequently manifests as Heart Failure (HF), a major limitation to effective cancer therapy. Sodium–glucose cotransporter 2 (SGLT2) inhibitors have demonstrated robust HF risk reduction across diverse populations, including patients receiving various chemotherapeutic regimens; however, their impact specifically in anthracycline-exposed patients remains uncertain. Purpose To evaluate the association between SGLT2 inhibitor use and HF outcomes among anthracycline-exposed patients, a population not previously studied independently in chemotherapy-related cardiotoxicity research. Methods Databases were searched from inception to February 2026 to identify studies comparing SGLT2 inhibitor use versus no SGLT2 therapy in patients receiving anthracyclines. The review was conducted and reported in accordance with PRISMA guidelines. Eligible studies reporting adjusted risk estimates for incident HF or Hospitalisation for Heart Failure (HHF) were included. The primary outcomes were incident HF and HHF. Adjusted hazard ratios [HRs] were extracted for all included studies. Random-effects meta-analysis was performed using restricted maximum likelihood (REML) with Hartung–Knapp–Sidik–Jonkman (HKSJ) adjustment to improve inference under uncertainty in between-study variance. Sensitivity analysis was conducted using a leave-one-out approach, with sequential exclusion of the highest-weight study. Results Seven retrospective studies comprising 3,765 patients were included (Figure 1). Six studies contributed to each outcome analysis. SGLT2 inhibitor use was associated with a significant reduction in incident HF [HR 0.44, 95% CI 0.22–0.89; p=0.03; I²=78%] (Figure 2A). A significant reduction in HHF was also observed [HR 0.34, 95% CI 0.14–0.83; p=0.03; I²=55%] (Figure 2B). Sensitivity analysis excluding the highest-weight study yielded consistent results for incident HF [HR 0.38, 95% CI 0.16–0.91; p=0.04; I²=68%]. Conclusion In patients receiving anthracyclines, SGLT2 inhibitor use was associated with significantly lower risks of incident HF and HHF. Despite the observational design and moderate heterogeneity, these findings suggest a potentially clinically meaningful cardioprotective role and support the need for prospective randomised controlled trials in this high-risk population.