Summary: In patients with type 2 diabetes and stable coronary artery disease, four years of dapagliflozin raised coronary flow reserve by 34% and reduced epicardial adipose tissue by 29%, an effect that appeared independent of weight loss.
PICO Summary
| Element | Detail |
|---|---|
| Population | Patients with type 2 diabetes and stable coronary artery disease (DAPAHEART follow-up; pilot). |
| Intervention | Dapagliflozin 10 mg daily; randomised 4-week phase then open treatment to 4 years. |
| Comparison | Placebo during the 4-week double-blind phase; all crossed to dapagliflozin thereafter. |
| Outcome | At 4 years CFR rose 34.4% (2.15 ± 0.19 to 2.85 ± 0.26; p=0.001) and EAT thickness fell 29.2% (p=0.03). BMI fell but did not correlate with EAT change (R²=0.07; p=0.5), suggesting a weight-independent effect. |
DAPAHEART follow-up: dapagliflozin and coronary flow reserve
Pilot RCT · type 2 diabetes + stable CAD · 4 years
Four years of dapagliflozin raised coronary flow reserve by 34% and shrank epicardial fat by 29% in type 2 diabetes with stable CAD. The epicardial-fat change did not track with weight loss, hinting at a direct, weight-independent effect, though this is a small uncontrolled pilot on imaging surrogates.
Expert Commentary
I no longer need persuading that SGLT2 inhibitors help the diabetic heart, since the outcome trials settled that, so I read this study not for whether to prescribe but for why the class works. On that mechanistic question it is genuinely satisfying: a one-third improvement in coronary flow reserve and a substantial regression of epicardial fat give me a coherent tissue-level story for the event reductions seen in the big trials, and the hint that the epicardial-fat effect is weight-independent fits the idea of a direct anti-inflammatory action. I hold the findings lightly as evidence, though, because this is a small pilot built on imaging surrogates, and after four weeks the placebo group crossed over, so the four-year comparison has no concurrent control. The weight-independence analysis was also almost certainly underpowered. Can I use this with my patients? It changes nothing in my prescribing, which is already guideline-driven, but it does give me a more persuasive mechanistic narrative when I explain to a patient with diabetes and coronary disease why this drug protects their heart. CFR and epicardial fat stay research tools, not clinic targets.
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