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

Methods

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).

这项开放标签的平行随机对照试验（RCT）招募了45名高风险参与者（年龄18-75岁），这些参与者均来自复旦大学中山医院内分泌科门诊（2022年8月至2024年11月），他们患有2型糖尿病（HbA1c 53.0-91.3 mmol/mol [7.0-10.5%]）且左心室射血分数（LVEF）>50%。

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).

参与者通过中央化的iClinicalStation系统按照1:1的比例通过计算机生成的序列进行随机分配（分配隐藏，由不参与结果评估的独立人员执行）。

They received canagliflozin 100 mg/day (n=23) or sitagliptin 100 mg/day (n=22) for 26 weeks.

他们接受每天100毫克的canagliflozin（n=23）或每天100毫克的sitagliptin（n=22）治疗26周。

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.

与开放标签设计一致，参与者和护理提供者知道治疗分配；然而，结果评估者（放射科医生，超声医师）和数据分析人员对组别分配保持盲态，以最小化偏倚。

The primary endpoint was CMR-quantified extracellular volume (ECV) change.

主要终点是通过心脏磁共振成像（CMR）定量的细胞外体积（ECV）变化。

Secondary outcomes included ventricular structure and function parameters, for example, left ventricular end-diastolic volume, left ventricular end-diastolic diameter, LVEF, etc. RESULTS: Among 67 individuals screened, 45 completed the intention-to-treatanalysis (age 60.4 ± 9.7 years, BMI 26.4 ± 2.6 kg/m2, HbA1c 63.0 ± 8.7 mmol/mol [7.9 ± 0.8%]).

次要结果包括心室结构和功能参数，例如左心室舒张末期容积、左心室舒张末期直径、LVEF等。结果：在67名接受筛查的个体中，有45人完成了意向治疗分析（年龄60.4 ± 9.7岁，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<0.001).

在26周时，与西格列汀相比，卡格列净显著降低了ECV的主要结果（调整后的平均差异[AMD]：-3.67%；95%置信区间-5.33, -2.01；p<0.001）。

Significant improvements were also observed in cardiac structure, including 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).

在心脏结构方面也观察到显著改善，包括左心室舒张末期容积（平均差异（AMD）：-20.72毫升；95%置信区间（CI）-36.30至-5.14；p=0.010）和超声心动图测量的舒张末期直径（AMD：-2.82毫米；95% CI -4.95至-0.70；p=0.010）。

Both groups showed comparable reductions in HbA1c (both Δ 0.7%, inter-group p=0.972).

两组在糖化血红蛋白（HbA1c）的降低上显示出可比性（两组均降低0.7%，组间比较p=0.972）。

conclusions/interpretation

This study demonstrates that 26 weeks of canagliflozin significantly reduces myocardial fibrosis, as assessed by CMR-derived ECV, in individuals with type 2 diabetes at high cardiovascular risk, providing imaging evidence for SGLT2 inhibitor cardiovascular protection mechanisms.

本研究显示，在高心血管风险的2型糖尿病患者中，经过26周的卡格列净治疗显著减少了心肌纤维化，通过CMR衍生的ECV评估，为SGLT2抑制剂的心血管保护机制提供了影像学证据。

trial_registration

ClinicalTrials.gov NCT05367063 FUNDING: This study was financially supported by the National Key Research and Development programme (2023YFA1802000), the National Natural Science Foundation of China (Youth Fund 82200909), the Young and Middle-aged Diabetes project from the Bethune Foundation (Z04JKM2022E002), the Joint Research Development project between Shenkang and United Imaging on Clinical Research and Translation (SKLY2022CRT201), the Shanghai Municipal 'Explorer plan' (the second batch) project in 2024 (24TS1411000) and the Shanghai pujiang programme (21PJD012).

ClinicalTrials.gov NCT05367063 资助信息：本研究得到了国家重点研发计划（2023YFA1802000）、国家自然科学基金（青年基金82200909）、白求恩基金会中青年糖尿病项目（Z04JKM2022E002）、申康与联影医疗在临床研究与转化方面的联合研发项目（SKLY2022CRT201）、2024年上海市'探索计划'（第二批）项目（24TS1411000）以及上海市浦江人才计划（21PJD012）的财政支持。