Summary: In the 4-year DAPAHEART follow-up in type 2 diabetes with stable coronary disease, dapagliflozin increased coronary flow reserve by 34.4% and reduced epicardial adipose tissue by about 29%, with the fat reduction appearing independent of weight loss.
PICO Summary
| Element | Detail |
|---|---|
| Population | Patients with type 2 diabetes and stable coronary artery disease; DAPAHEART pilot, single-centre, with PET/CT imaging. |
| Intervention | Dapagliflozin 10 mg; coronary flow reserve and epicardial fat measured at baseline, 4 weeks, and 4 years (placebo group later crossed to dapagliflozin). |
| Comparison | Initial placebo, then within-patient change over 4 years. |
| Outcome | Coronary flow reserve rose 34.4% at 4 years (2.15±0.19 to 2.85±0.26; p=0.001) with a 29.18% reduction in epicardial adipose thickness (p=0.03). BMI fell in all patients, but BMI and epicardial-fat changes were not correlated, suggesting a weight-independent effect. The crossover group showed similar changes after starting treatment. |
DAPAHEART 4-Year Follow-up
Pilot RCT · type 2 diabetes + CAD · 4 years
Over 4 years, dapagliflozin raised coronary flow reserve by 34.4% and cut epicardial fat by about 29%, with the fat reduction uncorrelated with weight loss.
Expert Commentary
This is a mechanistically satisfying study that helps answer why SGLT2 inhibitors protect the heart, not merely that they do. Coronary flow reserve is a meaningful surrogate for microvascular health, and a 34% improvement sustained over four years is substantial, plausibly shifting patients from an abnormal to a more normal range, while the parallel fall in epicardial adipose tissue offers a coherent mechanism, less local inflammation around the coronary arteries. The observation that epicardial-fat reduction did not track with BMI change is the most interesting detail, hinting at a direct effect on this metabolically active depot rather than a simple consequence of weight loss. The honest constraints are important: this is a small pilot with imaging endpoints rather than clinical events, the placebo-then-crossover design weakens the comparator, and coronary flow reserve, however predictive, is not a heart attack avoided. Can I use this with my patients? Supportively. It strengthens the rationale I already follow for favouring SGLT2 inhibitors in diabetic patients with cardiovascular risk and for continuing them long-term, while I remain clear that the hard outcome trials, not this surrogate study, justify the indication.
References
Cinti F, Morciano C, Guarneri A, et al. Coronary flow reserve increase after 4-year dapagliflozin treatment in patients with type 2 diabetes: the DAPAHEART follow-up study. Cardiovasc Diabetol. 2025;24(1):351. doi:10.1186/s12933-025-02912-4