Abstract Body (Do not enter title and authors here): Background: Cancer therapies, including anthracyclines and tyrosine kinase inhibitors, can induce cardiotoxic effects, increasing the incidence of heart failure (HF). With improvements in cancer survival rates, the focus has shifted towards minimizing non-cancer-related morbidities and improving overall quality of life. SGLT2 inhibitors (SGLT2i) have demonstrated efficacy in reducing cardiovascular events, particularly HF, in patients with and without diabetes. Given their dual cardioprotective and anticancer properties, these drugs present a promising therapeutic option in the cardio-oncology field. Preclinical studies have shown that SGLT2i, especially canagliflozin, can impede tumor growth in various cancer models.

Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines. Four studies were identified from three databases up to May 2024: MEDLINE/PubMed, Scopus, and the Cochrane Central Register of Controlled Trials. The SGLT2i used in these studies included canagliflozin, dapagliflozin, and empagliflozin. The total sample size was 10,775 patients, with 1,649 in the SGLT2i group and 9,126 in the control group. Outcomes analyzed were hospitalizations for HF, total adverse events, and all-cause mortality using R/R Studio.

Results: SGLT2i significantly reduced the risk of hospitalizations for HF compared to control (OR: 0.50; 95% CI: 0.38–0.66, p < 0.01), with significant heterogeneity observed (I² = 71%, p = 0.02). The incidence of total adverse events was lower in the SGLT2i group (OR: 0.99; 95% CI: 0.84–1.16, p < 0.01), with high heterogeneity noted (I² = 98%, p < 0.01). SGLT2i showed a trend towards reduced all-cause mortality but was not statistically significant (OR: 1.01; 95% CI: 0.87–1.18, p < 0.01), and high heterogeneity was present (I² = 98%, p < 0.01).

Conclusions: SGLT2i use in cancer patients is associated with a significant reduction in hospitalizations for HF. While there is a trend towards reduced all-cause mortality and total adverse events, the results are not statistically significant. The high heterogeneity in the analyzed studies suggests variability in patient populations and study designs, indicating a need for further research to confirm these findings.