# Comparison of ischemic cardiovascular events between dapagliflozin and empagliflozin in combination with metformin: A nationwide population-based cohort study

**Authors:** Hayeon Kim, Seung Won Lee, Yejee Lim, Nayoung Han, Suin Kang, Youngjoo Byun, Kyungim Kim

PMC · DOI: 10.1371/journal.pone.0333604 · PLOS One · 2025-10-16

## TL;DR

This study compares dapagliflozin and empagliflozin in type 2 diabetes patients to see if one is better at preventing heart and blood vessel issues when used with metformin.

## Contribution

It provides real-world evidence on the comparative effectiveness of two SGLT-2 inhibitors for cardiovascular outcomes in Asian patients with T2DM.

## Key findings

- No significant difference in composite ischemic CVD events between dapagliflozin and empagliflozin when combined with metformin.
- Findings suggest similar cardiovascular risk profiles for both drugs in real-world settings.
- Results were consistent across individual components of CVD events and mortality.

## Abstract

The comparative effectiveness of individual sodium–glucose cotransporter-2 inhibitors (SGLT-2is) in preventing ischemic cardiovascular disease (CVD) remains uncertain. Thus, this study compared the incidence of ischemic CVD events in patients with type 2 diabetes mellitus (T2DM) treated with dapagliflozin or empagliflozin in combination with metformin. This retrospective cohort study analyzed national claims data from the Korean National Health Insurance Service. Patients with T2DM who received dapagliflozin or empagliflozin, combined with metformin, between 2014 and 2019 were included. The primary outcome was composite ischemic CVD events, defined as myocardial infarction, ischemic stroke, or coronary revascularization. Secondary outcomes included each component of composite ischemic CVD events, unstable angina, and all-cause mortality. Hazard ratios (HRs) and confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusting for covariates in three stepwise models: Model 1 (age and sex), Model 2 (Model 1 variables plus patient characteristics), and Model 3 (Model 2 variables plus clinical parameters). In Model 3, after full adjustment for systolic blood pressure, low-density lipoprotein cholesterol, fasting blood glucose, and serum creatinine, no significant difference was observed in the incidence of composite ischemic CVD events between dapagliflozin and empagliflozin when each was used in combination with metformin (adjusted HR 0.50, 95% CI: 0.24–1.03). Additionally, no significant differences were observed in individual components of composite ischemic CVD events, unstable angina, and all-cause mortality. These real-world findings may help in selecting an SGLT-2is subtype for CVD prevention in Asian patients with T2DM.

## Linked entities

- **Chemicals:** dapagliflozin (PubChem CID 9887712), empagliflozin (PubChem CID 11949646), metformin (PubChem CID 4091)
- **Diseases:** type 2 diabetes mellitus (MONDO:0005148), myocardial infarction (MONDO:0005068), ischemic stroke (MONDO:1060198), unstable angina (MONDO:0006805)

## Full-text entities

- **Diseases:** T2DM (MESH:D003924), ischemic stroke (MESH:D002544), myocardial infarction (MESH:D009203), unstable angina (MESH:D000789), CVD (MESH:D002318), ischemic (MESH:D002545)
- **Chemicals:** SGLT-2is (-), empagliflozin (MESH:C570240), glucose (MESH:D005947), metformin (MESH:D008687), creatinine (MESH:D003404), dapagliflozin (MESH:C529054)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

71 references — full list in the complete paper: https://tomesphere.com/paper/PMC12530601/full.md

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Source: https://tomesphere.com/paper/PMC12530601