Related Experiment Video
Updated: May 16, 2026
In Silico Clinical Trials for Cardiovascular Disease
Published on: May 27, 2022
SGLT2 Inhibitors in Cardio-Oncology: A Systematic Review and Meta-Analysis
Luigi Spadafora1, Marco Bernardi1, Gianmarco Sarto2
1Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy; UOC UTIC Emodinamica e Cardiologia, Santa Maria Goretti Hospital, Latina, Italy.
Background:
According to available evidence, sodium-glucose cotransporter-2 inhibitors (SGLT2i) may confer cardioprotection in patients with cancer undergoing chemotherapy.
Objectives:
The objective of the study was to evaluate the impact of SGLT2i on all-cause mortality and heart failure (HF) outcomes in this population.
Methods:
We searched PubMed, Cochrane CENTRAL, and Embase through August 2025 for studies of SGLT2i in adult patients with cancer. Random-effects models were used to pool effects for all-cause mortality and an HF composite (new-onset HF and/or HF hospitalization) in cancer patients >18 years. Meta-regression tested effect modification by beta-blockers, statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, age, and sex.
Results:
Thirteen observational studies were included, for a total of 107,126 patients. The median age was 67.6 years (IQR: 62.5-71.0); median follow-up was 24 months (IQR: 19.2-29.0), nearly all patients had diabetes mellitus. SGLT2i were associated with lower all-cause mortality (risk ratio [RR]: 0.47; 95% CI: 0.38-0.58; I2 = 96.30%; P < 0.001), with no effect modification by background therapies, age, or sex (all P > 0.05). The HF composite was also significantly reduced (RR: 0.48; 95% CI: 0.29-0.78; I2 = 87.01%), again with no evidence that background therapies modified the effect (all P > 0.05). Risk of atrial fibrillation/atrial flutter was lower with SGLT2i (RR: 0.57; 95% CI: 0.42-0.76; I2 = 66.4%; P < 0.001). Safety outcomes were not increased in the SGLT2i arm.
Conclusions:
In patients with cancer, SGLT2i appear safe and are associated with fewer deaths and HF events, although substantial heterogeneity was observed across studies. Randomized controlled trials are warranted to confirm these hypothesis-generating findings.
Insights
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) show promise in reducing mortality and heart failure (HF) events in cancer patients. These findings suggest SGLT2i may offer significant cardioprotective benefits for this vulnerable population.
Area of Science:
- Cardiology
- Oncology
- Pharmacology
Background:
- Emerging evidence suggests sodium-glucose cotransporter-2 inhibitors (SGLT2i) may provide cardioprotective effects in cancer patients undergoing chemotherapy.
- Cancer patients face increased risks of cardiovascular complications, necessitating novel therapeutic strategies.
Purpose of the Study:
- To evaluate the impact of SGLT2i on all-cause mortality.
- To assess the effect of SGLT2i on heart failure (HF) outcomes, including new-onset HF and HF hospitalizations.
Main Methods:
- A systematic literature search was conducted across PubMed, Cochrane CENTRAL, and Embase up to August 2025.
- Random-effects models were employed to pool data from 13 observational studies involving 107,126 cancer patients.
- Meta-regression analysis explored potential effect modification by concomitant medications, age, and sex.
Main Results:
- SGLT2i use was associated with a significant reduction in all-cause mortality (RR: 0.47; 95% CI: 0.38-0.58) and a composite HF outcome (RR: 0.48; 95% CI: 0.29-0.78).
- A notable decrease in the risk of atrial fibrillation/atrial flutter was observed with SGLT2i (RR: 0.57; 95% CI: 0.42-0.76).
- No significant effect modification was found for background therapies, age, or sex on mortality or HF outcomes.
Conclusions:
- SGLT2i appear to be safe and effective in reducing mortality and HF events in cancer patients.
- Substantial heterogeneity across studies necessitates cautious interpretation of findings.
- Further randomized controlled trials are required to validate these promising results.
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