Summary: In 100 patients with type 2 diabetes and heart failure with preserved ejection fraction, 12 months of dapagliflozin 10 mg daily reduced cardiac MRI extracellular volume fraction, a surrogate marker of myocardial fibrosis, by a mean of 3.5% versus 0.8% with placebo (p<0.001). Secondary imaging, glycaemic, and functional measures also improved. Clinical endpoints were not assessed.
PICO Summary
| Element | Detail |
|---|---|
| Population | 100 patients with type 2 diabetes and heart failure with preserved ejection fraction; multicentre, double-blind, placebo-controlled randomised controlled trial, stratified by baseline extracellular volume fraction (Oman). |
| Intervention | Dapagliflozin 10 mg orally once daily for 12 months (n=50). |
| Comparison | Matching placebo for 12 months (n=50). |
| Outcome | Primary, change in cardiac MRI extracellular volume fraction (myocardial fibrosis): -3.5% (95% CI -4.2 to -2.8) with dapagliflozin versus -0.8% (95% CI -1.3 to -0.4) with placebo, p<0.001. Secondary: left ventricular mass index -8.2 versus -2.1 g/m² (p=0.002); HbA1c -1.2% versus -0.4% (p=0.01); 6-minute walk distance +45 m versus +10 m (p=0.01). No clinical event outcomes, absolute risk reduction, or number needed to treat were reported. |
Dapagliflozin and myocardial fibrosis in diabetic HFpEF
RCT · type 2 diabetes + HFpEF · 12 months
Over 12 months, dapagliflozin reduced an MRI surrogate of myocardial fibrosis (ECV) far more than placebo (-3.5% vs -0.8%). Imaging surrogate only; no clinical event outcomes were assessed.
Expert Commentary
This small double-blind trial provides mechanistically interesting evidence that dapagliflozin can regress an imaging surrogate of myocardial fibrosis in diabetic HFpEF, and the effect on extracellular volume fraction was both statistically convincing and internally consistent with improvements in left ventricular mass, glycaemic control, and walk distance. The verdict, however, must remain cautious. The primary endpoint is a cardiac MRI surrogate, not a clinical outcome such as hospitalisation or death, and a regression of 3.5% in extracellular volume over 12 months, while plausible, is on the larger side for an antifibrotic signal and was generated in a single 100-patient programme that has not yet been replicated. The principal limitation is therefore one of evidentiary weight: surrogate gains in a modest, single-centre-network sample cannot by themselves establish disease modification, and the absence of reported event data leaves the patient-important benefit unquantified. Can I use this with my patients? For most people with type 2 diabetes and HFpEF, dapagliflozin is already guideline-directed therapy on the strength of outcome trials, so this study reinforces rather than changes practice; it does not yet justify using fibrosis regression as a treatment target. Larger trials with clinical endpoints and independent imaging adjudication should confirm whether the fibrosis signal translates into outcomes that patients can feel.
References
Albulushi A, Askari KM, Al-Abedi AM, Al-Kulaibi MA, Hasan MS, Hosseini Z, et al. Impact of SGLT2 inhibitors on myocardial fibrosis in diabetic HFpEF: a longitudinal study. Eur J Med Res. 2025;30(1):592. doi:10.1186/s40001-025-02834-7
