# The impact of SGLT2i on the outcome of advanced lung cancer in patients with diabetes

**Authors:** Jindong Chen, Hao Wang, Conghui Shang, Zixu Fan, Ziyi Sheng, Tianqing Chu, Min Zhang, Liang Zhao

PMC · DOI: 10.3389/fonc.2026.1759702 · Frontiers in Oncology · 2026-02-20

## TL;DR

This study found that SGLT2i, a diabetes drug, may improve survival in advanced lung cancer patients with diabetes without increasing heart risks.

## Contribution

The study is the first to show SGLT2i's potential survival benefit in advanced lung cancer patients with diabetes.

## Key findings

- SGLT2i use was linked to a 44% lower risk of death in patients with advanced lung cancer and diabetes.
- SGLT2i did not significantly affect the rate of major adverse cardiovascular events.
- Post-MACE survival was not significantly different between SGLT2i and control groups.

## Abstract

Sodium-glucose cotransporter-2 inhibitors (SGLT2i), a novel pharmacological agent for diabetes and heart failure, may influence oncologic outcomes. Their role in advanced lung cancer patients with diabetes is unclear. Our study aims to evaluate SGLT2i’s effects in this population.

We performed a retrospective analysis of advanced lung cancer patients diagnosed with diabetes at our center between July 2020 and July 2024. The case cohort include patients who received SGLT2i, while the control cohort did not. The primary endpoint was overall mortality, and the secondary endpoint was a composite of cardiac events.

The cohort included 188 patients, with 94 cases and 94 controls. Over a median follow-up of 16 months, the use of SGLT2i was significantly associated with improved survival for advanced lung cancer with diabetes. (hazard ratio, (HR) 0.56; 95% CI 0.35–0.87, P = 0.009). The survival rate was lower in major adverse cardiovascular events (MACE) group than non-MACE group, however the differences were not statistically significant (HR 1.69; 95% CI 0.96– 2.97, P = 0.067). During follow-up, the incidence of MACE (24 cases in total, with new-onset atrial fibrillation/flutter being the most common) did not differ significantly between SGLT2i and control groups (11.7% vs. 13.8%; P = 0.662).

In advanced lung cancer patients with diabetes, SGLT2i was associated with a lower all-cause mortality rate. Yet SGLT2i had insignificant impact on the incidence of MACE and the post-MACE survival.

## Linked entities

- **Diseases:** diabetes (MONDO:0005015), lung cancer (MONDO:0005138), atrial fibrillation (MONDO:0004981), heart failure (MONDO:0005252)

## Full-text entities

- **Genes:** PRKAB1 (protein kinase AMP-activated non-catalytic subunit beta 1) [NCBI Gene 5564] {aka AMPK, HAMPKb}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, TENM1 (teneurin transmembrane protein 1) [NCBI Gene 10178] {aka ODZ1, ODZ3, TEN-M1, TEN1, TNM, TNM1}, SLC5A2 (solute carrier family 5 member 2) [NCBI Gene 6524] {aka SGLT2}, TNNT2 (troponin T2, cardiac type) [NCBI Gene 7139] {aka CMD1D, CMH2, CMPD2, LVNC6, RCM3, TnTC}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}
- **Diseases:** heart disease (MESH:D006331), acute kidney injury (MESH:D058186), coronary artery disease (MESH:D003324), myocarditis (MESH:D009205), diabetic ketoacidosis (MESH:D016883), myocardial injury (MESH:D009202), breast cancer (MESH:D001943), obesity (MESH:D009765), heart and kidney complications (MESH:D007674), heart failure (MESH:D006333), malignant arrhythmias (MESH:D001145), type 2 diabetes (MESH:D003924), hypoxia (MESH:D000860), NSCLC (MESH:D002289), ventricular tachycardia (MESH:D017180), ketoacidosis (MESH:D007662), Stage III-IV (MESH:D062706), metabolic abnormalities (MESH:D008659), ventricular fibrillation (MESH:D014693), cardiotoxicity (MESH:D066126), acute coronary syndrome (MESH:D054058), died (MESH:D003643), diabetic complications (MESH:D048909), small cell lung cancer (MESH:D055752), hyperinsulinemia (MESH:D006946), hypertension (MESH:D006973), diabetic cardiomyopathy (MESH:D058065), hyperglycemia (MESH:D006943), SCLC (MESH:D018288), fibrosis (MESH:D005355), inflammation (MESH:D007249), atrial fibrillation/flutter (MESH:D001282), insulin resistance (MESH:D007333), AV block (MESH:D054537), Urinary tract infection (MESH:D014552), ACS (MESH:D000168), dehydration (MESH:D003681), cancer (MESH:D009369), Diabetic (MESH:D003920), atrial fibrillation (MESH:D001281), hypoglycemia (MESH:D007003), MACE (MESH:D002318), Lung cancer (MESH:D008175)
- **Chemicals:** insulin (MESH:D007328), glucose (MESH:D005947), creatinine (MESH:D003404), ACEI (-), Dapagliflozin (MESH:C529054), lactate (MESH:D019344)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** A1C

## Full text

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## Figures

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## References

30 references — full list in the complete paper: https://tomesphere.com/paper/PMC12962895/full.md

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Source: https://tomesphere.com/paper/PMC12962895