Canagliflozin attenuates CMR-quantified myocardial fibrosis in individuals with type 2 diabetes mellitus at high cardiovascular risk: a randomised open-label controlled trial

We aimed to investigate canagliflozin’s effects on myocardial fibrosis, cardiac structure and function, and microcirculation in high-cardiovascular-risk type 2 diabetes mellitus through cardiac magnetic resonance (CMR) quantification, while investigating the cardiovascular protective mechanisms of sodium–glucose cotransporter 2 (SGLT2) inhibitors. This open-label parallel RCT recruited 45 high-risk participants (18–75 years) with type 2 diabetes (HbA1c 53.0–91.3 mmol/mol [7.0–10.5%]) and left ventricular ejection fraction (LVEF) >50% from the Endocrinology Outpatient Clinic of Zhongshan Hospital, Fudan University (August 2022 to November 2024). Participants were 1:1 randomised via a computer-generated sequence through the centralised iClinicalStation system (allocation concealed, performed by independent personnel not involved in outcome assessment). They received canagliflozin 100 mg/day (n=23) or sitagliptin 100 mg/day (n=22) for 26 weeks. Consistent with the open-label design, participants and care providers were aware of treatment assignments; however, outcome assessors (radiologists, sonographers) and data analysts remained blinded to group allocation to minimise bias. The primary endpoint was CMR-quantified extracellular volume (ECV) change. Secondary outcomes included ventricular structure and function parameters, for example, left ventricular end-diastolic volume, left ventricular end-diastolic diameter, LVEF, etc. Among 67 individuals screened, 45 completed the intention-to-treat analysis (age 60.4 ± 9.7 years, BMI 26.4 ± 2.6 kg/m2, HbA1c 63.0 ± 8.7 mmol/mol [7.9 ± 0.8%]). At 26 weeks, compared with sitagliptin, canagliflozin significantly reduced the primary outcome of ECV (adjusted mean difference [AMD]: −3.67%; 95% CI −5.33, −2.01; p