# SGLT-2 inhibitors in prevention of chemotherapy-induced cardiotoxicity: systematic review and meta-analysis

**Authors:** Soomal Rafique, Michael Buhnerkempe, Yansoun Elmasry, Abhishek Kulkarni, Krishna Rao, Mukul Bhattarai

PMC · DOI: 10.1093/ehjopen/oeag012 · European Heart Journal Open · 2026-01-31

## TL;DR

This study finds that SGLT2 inhibitors may protect cancer patients from chemotherapy-related heart damage and reduce mortality.

## Contribution

The study is the first to systematically evaluate and meta-analyze the cardioprotective effects of SGLT2 inhibitors in chemotherapy patients.

## Key findings

- SGLT2 inhibitors significantly reduced all-cause mortality in cancer patients undergoing chemotherapy.
- Use of SGLT2 inhibitors was associated with fewer cardiac events and heart failure hospitalizations.
- The findings suggest SGLT2 inhibitors could be integrated into cardio-oncology strategies.

## Abstract

Chemotherapy is associated with significant cardiotoxicity. Although other guideline directed medications for heart failure are effective in managing or preventing these cardiotoxic effects, the potential role of sodium-glucose cotransporter-2 (SGLT2) inhibitors remain incompletely understood.

This study aims to systematically review high-quality studies to evaluate the cardiovascular outcomes associated with SGLT2 inhibitor use in cancer patients undergoing chemotherapy.

We conducted a meta-analysis of cohort studies comparing cardiovascular outcomes between cancer patients receiving SGLT2 inhibitors and those not receiving SGLT2 inhibitors. Cochrane Central Register, clinicaltrials.gov, PubMed, Embase, and Google Scholar were searched from inception to May 2025. Primary outcome was all-cause mortality. Secondary outcomes included cardiac events, and cardiac dysfunction. We used fixed and random effect binomial meta-analysis fit using the Mantel–Haenszel method for each outcome of interest. All analyses were conducted using the ‘meta’ package in R Statistical Software. Eleven cohort studies comprising 2 689 260 patients were included, of whom 29 958 received SGLT2 inhibitors. SGLT2 inhibitor use was significantly associated with reduced all-cause mortality (OR 0.27, 95% CI 0.25–0.28), cardiac events (OR 0.49, 95% CI 0.49–0.53), cardiac dysfunction (OR 0.62, 95% CI 0.56–0.69), and heart failure hospitalizations (HFH; OR 0.67, 95% CI 0.61–0.75) compared to non-use.

SGLT2 inhibitors demonstrate robust cardioprotective effects in cancer patients receiving chemotherapy, significantly reducing mortality, HFH, and major cardiac events. These findings support the integration of SGLT2 inhibitors into cardio-oncology strategies, particularly for patients at high risk of chemotherapy-induced cardiotoxicity.

## Linked entities

- **Diseases:** heart failure (MONDO:0005252)

## Full-text entities

- **Genes:** VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, PRKAA2 (protein kinase AMP-activated catalytic subunit alpha 2) [NCBI Gene 5563] {aka AMPK, AMPK2, AMPKa2, PRKAA}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, SLC5A2 (solute carrier family 5 member 2) [NCBI Gene 6524] {aka SGLT2}
- **Diseases:** Cardiotoxicity (MESH:D066126), HCC (MESH:D006528), renal or bladder cancer (MESH:D001749), nonsmall cell lung cancer (MESH:D002289), RCC (MESH:D002292), left-ventricular systolic dysfunction (MESH:D018487), type 2 diabetes (MESH:D003924), HFH (MESH:D006333), arrhythmias (MESH:D001145), breast cancer (MESH:D001943), cardiomyopathy (MESH:D009202), acute kidney injury (MESH:D058186), DKA (MESH:D016883), stroke (MESH:D020521), Cardiac dysfunction (MESH:D006331), acute myocardial infarction (MESH:D009203), CTRCD (MESH:D016609), infections (MESH:D007239), cardiovascular comorbidity (MESH:D002318), diabetes (MESH:D003920), atrial fibrillation (MESH:D001281), Cancer (MESH:D009369), ischaemic stroke (MESH:D002544), urinary tract infection (MESH:D014552), DM2 (MESH:D009223), inflammation (MESH:D007249), death (MESH:D003643)
- **Chemicals:** glucose (MESH:D005947), reactive oxygen species (MESH:D017382), empagliflozin (MESH:C570240), trastuzumab (MESH:D000068878), angiotensin receptor-neprilysin inhibitors (-), platinum (MESH:D010984), doxorubicin (MESH:D004317), anthracycline (MESH:D018943)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12930847/full.md

## References

35 references — full list in the complete paper: https://tomesphere.com/paper/PMC12930847/full.md

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Source: https://tomesphere.com/paper/PMC12930847