Cardiovascular benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors have been observed in outcome trials, yet direct imaging evidence of myocardial structural changes remains limited. A randomized, open-label, parallel-group trial published in Diabetologia examined the effects of canagliflozin on myocardial fibrosis, cardiac structure, function, and microcirculation in individuals with type 2 diabetes (T2DM) at elevated cardiovascular risk.
The study enrolled adults aged 18 to 75 years with glycated hemoglobin (HbA1c) levels between 53.0 and 91.3 mmol/mol (7.0-10.5%) and preserved left ventricular ejection fraction (LVEF >50%). Participants were recruited from the Endocrinology Outpatient Clinic of Zhongshan Hospital, Fudan University, between August 2022 and November 2024. Using centralized computer-generated allocation, 45 individuals were randomized in a 1:1 ratio to receive canagliflozin 100 mg daily (n = 23) or sitagliptin 100 mg daily (n = 22) for 26 weeks. The primary outcome was change in extracellular volume (ECV) quantified by cardiac magnetic resonance (CMR). Imaging assessors and data analysts remained blinded to treatment assignment.
Of 67 individuals screened, 45 were included in the intention-to-treat analysis (mean age 60.4 ± 9.7 years; body mass index 26.4 ± 2.6 kg/m²; HbA1c 63.0 ± 8.7 mmol/mol [7.9 ± 0.8%]). At 26 weeks, canagliflozin produced a greater reduction in ECV than sitagliptin (adjusted mean difference −3.67%; 95% confidence interval −5.33, −2.01; p<0.001). Decreases were also observed in left ventricular end-diastolic volume (AMD −20.72 ml; 95% CI −36.30, −5.14; p = 0.010) and echocardiography-derived end-diastolic diameter (AMD −2.82 mm; 95% CI −4.95, −0.70; p=0.010). Both treatment groups demonstrated comparable HbA1c reductions (Δ 0.7%; p = 0.972).
Twenty-six weeks of canagliflozin therapy reduced myocardial fibrosis, as reflected by CMR-derived extracellular volume, in individuals with T2DM at high cardiovascular risk. The findings provide imaging-based support for cardiovascular protection mechanisms associated with SGLT2 inhibitor therapy.
