The Effect of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors on Cardiovascular Outcomes in Cancer Patients With Type 2 Diabetes Mellitus: A Systematic Review.

Abstract

While the cardiovascular benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in patients with type 2 diabetes mellitus (T2DM) are well-established, their role in cancer patients with T2DM - a population at heightened risk of cardiovascular complications due to both malignancy and cardiotoxic therapies - remains unclear. This systematic review aimed to synthesize the existing evidence on the effects of SGLT2is on cardiovascular outcomes in this high-risk group. We conducted a comprehensive literature search across PubMed/MEDLINE, Embase, Scopus, and Web of Science following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Observational cohort studies and randomized controlled trials (RCTs) evaluating SGLT2is in adult cancer patients with T2DM were included. Data extraction and quality assessment (using the Newcastle-Ottawa Scale for cohort studies) were performed independently by two reviewers. Due to clinical and methodological heterogeneity, findings were synthesized narratively, with effect estimates [hazard ratios (HRs), odds ratios (ORs)] and 95% confidence intervals (CIs) reported. Nine studies (n = 162,605 participants) were included, comprising retrospective cohorts (n = 7) and population-based studies (n = 2). SGLT2i use was consistently associated with reduced all-cause mortality and heart failure (HF)-related hospitalizations. Benefits were particularly pronounced in patients exposed to anthracyclines or with pre-existing cardiovascular risk. Subgroup analyses suggested a dose-dependent survival advantage, while safety outcomes were comparable to non-users. Study quality was generally high, though heterogeneity precluded meta-analysis. SGLT2 inhibitors appear to confer significant cardiovascular protection in cancer patients with T2DM, particularly against mortality and HF. These findings support their cautious integration into cardio-oncology practice, though randomized trials are needed to confirm causality and optimize protocols. Clinicians should weigh individual risks, especially in immunocompromised patients, while researchers should prioritize prospective studies to clarify mechanisms and long-term effects.