EMERGING evidence continues to reshape the treatment landscape for heart failure with preserved ejection fraction (HFpEF), particularly in patients also living with Type 2 diabetes (T2D). Sodium–glucose co-transporter 2 (SGLT2) inhibitors have already shown cardiovascular benefit, but until now, their direct impact on myocardial fibrosis, an important driver of disease progression, has not been well defined. A recent study has found that dapagliflozin significantly reduces cardiac fibrosis in diabetic HFpEF patients, suggesting a potentially disease-modifying role.
This multicentre, double-blind, placebo-controlled trial enrolled 100 patients with both HFpEF and T2D. Participants were randomly assigned to receive either dapagliflozin 10 mg daily or placebo for 12 months. Patients were stratified by baseline extracellular volume fraction (ECV), a cardiac MRI-based measure of myocardial fibrosis. ECV was assessed at baseline, 6 months, and 12 months. Secondary outcomes included changes in left ventricular mass index (LVMI), HbA1c levels, and distance walked during a 6-minute walk test (6MWT).
At 12 months, patients treated with dapagliflozin showed a significantly greater reduction in myocardial fibrosis, with a mean ECV change of −3.5% (95% CI: −4.2–−2.8) versus −0.8% (95% CI: −1.3–−0.4) in the placebo group (p < 0.001). Improvements in LVMI (−8.2 g/m² vs. −2.1 g/m²; p=0.002), HbA1c (−1.2% vs. −0.4%; p=0.01), and 6MWT performance (+45 m vs. +10 m; p=0.01) were also significantly greater in the dapagliflozin group.
These findings highlight dapagliflozin’s potential to modify underlying disease processes in HFpEF patients with T2D by reversing myocardial fibrosis. While the sample size was modest and follow-up limited to one year, the data suggest meaningful benefits across structural, metabolic, and functional domains. In clinical practice, these results further support the inclusion of SGLT2 inhibitors as part of guideline-directed medical therapy, not only for symptom management but possibly for altering the disease course itself.
Reference
Albulushi A et al. Impact of SGLT2 inhibitors on myocardial fibrosis in diabetic HFpEF: a longitudinal study. Eur J Med Res. 2025;30(1):592.
