SGLT2 Inhibitors in Cardio-Oncology

Figure 1. All-Cause Mortality and Study-Level Meta-Regression Analyses (A) Random-effects meta-analysis (REML model) of SGLT2 inhibitors vs controls for all-cause mortality. (B) Univariable meta-regressions testing beta-blocker, ACEI/ARB, statin use, sex, and mean age as study-level moderators (effect per 10% or 10-year increase). ACEI/ARB = angiotensin-converting enzyme inhibitor or angiotensin receptor blocker; exp(ES) = exponentiated effect size; REML = restricted maximum likelihood; RR = risk ratio.

Figure 2. Heart Failure Composite and Study-Level Meta-Regression Analyses (A) Random-effects meta-analysis (REML model) of SGLT2 inhibitors vs controls for the composite of incident HF and/or HF hospitalization. (B) Univariable meta-regressions testing beta-blocker, ACEI/ARB, and statin use as study-level moderators (effect per 10% increase). HF = heart failure; other abbreviations as in Figure 1.

Figure 3. Forest Plots for Atrial Fibrillation/Atrial Flutter, Myocardial Infarction, and Stroke AF/AFL = atrial fibrillation/atrial flutter; other abbreviation as in Figure 1.

Figure 4. Random-Effects Meta-Analysis of the Association Between SGLT2 Inhibitors and AKI, UTI, and Sepsis Effect sizes are reported as exponentiated effect estimates (exp[ES]) with 95% CI. AKI = acute kidney injury; UTI = urinary tract infection; other abbreviation as in Figure 1.

Central Illustration. Potential Role of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Cancer Receiving Cardiotoxic Therapies Across observational studies, SGLT2i use was associated with reduced all-cause mortality and improved heart failure (HF) outcomes, with consistent findings across sensitivity analyses. These associations appeared independent of age, sex, and background cardioprotective therapies. Overall, the evidence remains observational and heterogeneous, and results should be considered hypothesis-generating. Ongoing randomized clinical trials are needed to clarify the role of SGLT2i as a cardioprotective strategy in cardio-oncology. AF/AFL = atrial fibrillation/atrial flutter; RR = risk ratio.