# Cardioprotective effect of diabetic medication on cancer patients undergoing proven cardiotoxic chemotherapy: a systematic review and meta-analysis

**Authors:** Abdelrahman El-Helbawy, Sara T. Zaki, Fouad Hanna, Mohamed Bassiouni, Khaled O. Yaseen, Amany H. Ali, Oliver M. Farid

PMC · DOI: 10.1186/s40959-025-00424-4 · 2026-01-15

## TL;DR

This study finds that diabetic medications, especially SGLT-2 inhibitors, may protect cancer patients from heart damage caused by certain chemotherapies.

## Contribution

The study provides new observational evidence that SGLT-2 inhibitors may reduce cardiotoxic effects in cancer patients undergoing chemotherapy.

## Key findings

- Diabetic medications may lower mortality, heart failure incidence, and exacerbation in cancer patients.
- SGLT-2 inhibitors showed a 50% reduction in mortality and 64% reduction in heart failure incidence.
- Hazard ratio analysis confirmed SGLT-2 inhibitors' cardioprotective effect in chemotherapy patients.

## Abstract

Multiple chemotherapeutic agents, such as anthracyclines, have recently shown a fatal potential for cardiotoxic effects in their patients. However, their efficacy is often hindered by their harmful adverse effects, mostly cardiotoxicity. DM medications such as metformin, SGLT-2 inhibitors, and GLP-1 receptor agonists have exhibited promising cardioprotective properties in rat clinical trials.

We conducted our study to investigate the observational association between diabetic medications and Cardioprotective effect in cancer patients treated with cardiotoxic chemotherapeutics.

A meta-analysis following PRISMA guidelines included observational studies comparing diabetic cancer patients treated with chemotherapy. Outcomes evaluated were heart failure (HF) incidence, HF exacerbation, atrial fibrillation (AF), hospitalization, and mortality. Data were independently extracted by five investigators from multiple databases up to January 20, 2025.

Eight studies involving 27,015 patients were included. DM medication use may be associated with lower mortality (OR 0.50, p < 0.00001), HF incidence (OR 0.36, p = 0.007), HF exacerbation (OR 0.58, p < 0.0001), although heterogeneity was significant. Subgroup analysis revealed that SGLT-2 inhibitors may be associated with reduced mortality by 50%, HF incidence by 64%, and HF exacerbation by 49%. Hazard ratio analysis indicated SGLT-2 inhibitors use was associated with lower mortality risk in patients receiving cardiotoxic chemotherapy (HR 0.58, p = 0.001).

Diabetic medications, particularly SGLT-2 inhibitors, may be associated with observational cardioprotective effect in cancer patients undergoing cardiotoxic chemotherapy. These findings highlight the need for further prospective trials to confirm subgroup benefits.

The online version contains supplementary material available at 10.1186/s40959-025-00424-4.

## Linked entities

- **Chemicals:** metformin (PubChem CID 4091)
- **Diseases:** heart failure (MONDO:0005252), atrial fibrillation (MONDO:0004981), cancer (MONDO:0004992), diabetes mellitus (MONDO:0005015)

## Full-text entities

- **Genes:** PRKAB1 (protein kinase AMP-activated non-catalytic subunit beta 1) [NCBI Gene 5564] {aka AMPK, HAMPKb}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, GCG (glucagon) [NCBI Gene 2641] {aka GLP-1, GLP1, GLP2, GRPP}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, SLC5A2 (solute carrier family 5 member 2) [NCBI Gene 6524] {aka SGLT2}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, MYD88 (MYD88 innate immune signal transduction adaptor) [NCBI Gene 4615] {aka IMD68, MYD88D, WM1}, GLP1R (glucagon like peptide 1 receptor) [NCBI Gene 2740] {aka GLP-1, GLP-1-R, GLP-1R}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}
- **Diseases:** cardiovascular (MESH:D002318), death (MESH:D003643), HF (MESH:D006333), DM (MESH:D009223), Diabetes Mellitus (MESH:D003920), ROBINS-I (MESH:C580335), hematological and solid malignancies (MESH:D019337), AF (MESH:D001281), Heart Fail (MESH:D055111), breast cancer (MESH:D001943), Cardiac Dysfunction (MESH:D006331), Arrhythmia (MESH:D001145), cardiomyopathy (MESH:D009202), cardiac inflammation (MESH:D007249), AIC (MESH:D066126), Acute Myocardial Infarction (MESH:D009203), pericarditis (MESH:D010493), hear t failure (MESH:D051437), ischemic stroke (MESH:D002544), Hypertension (MESH:D006973), mitochondrial dysfunction (MESH:D028361), genitourinary malignancies (MESH:D014565), myocarditis (MESH:D009205), cardiac arrest (MESH:D006323), lymphoma (MESH:D008223), leukemia (MESH:D007938), myocardial strain (MESH:D013180), type 2 diabetes mellitus (MESH:D003924), Cancer (MESH:D009369), AF/flutter (MESH:D001282), fibrosis (MESH:D005355)
- **Chemicals:** reactive oxygen species (MESH:D017382), aspirin (MESH:D001241), idarubicin (MESH:D015255), epirubicin (MESH:D015251), glucose (MESH:D005947), Calcium (MESH:D002118), donepezil (MESH:D000077265), lipid (MESH:D008055), ANTs (MESH:D018943), DOX (MESH:D004317), daunorubicin (MESH:D003630), DM (-), Metformin (MESH:D008687)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12853835/full.md

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Source: https://tomesphere.com/paper/PMC12853835