A Phase 4 interventional study of Canagliflozin 100mg or Sitagliptin 100mg in Type 2 Diabetes and Cardiovascular Risk, sponsored by Shanghai Zhongshan Hospital. Completed at 1 site in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2025-12-16.
Sponsored by Shanghai Zhongshan Hospital · Phase 4, Interventional, and Treatment
Recently, large clinical intervention studies have demonstrated the cardiovascular protective effects on of sodium-glucose cotransporter 2 inhibitors (SGLT2i) such as empagliflozin, dapagliflozin, and canagliflozin in reduction of cardiovascular and all-cause mortality, coincident with a significant reduction in heart failure hospitalizations. Therefore, SGLT2i had been recommended as a therapeutic drug for diabetic patients to reduce the occurrence of cardiovascular events. However, the mechanism of these benefits remains unclear at the present time.
Myocardial fibrosis is not only an important physiopathological mechanism of heart failure, but also has been shown to be closely associated with the risk of heart failure-related hospitalization and death, especially in patients with T2D. However, whether SGLT2i can exert cardioprotective effects by improving myocardial fibrosis remains to be further investigated. In recent years, the development of cardiac magnetic resonance (CMR) technology enables to detect focal and diffuse fibrosis in myocardial tissue, which makes it possible to systematically explore the role of SGLT2i on myocardial fibrosis. Although several studies including EMPA-HEART, SUGAR-DM-HF have explored the effects of SGLT2i on cardiac structure and function, these studies didn't reach consistent results. In addition, more scarce studies have investigated the effects of SGLT2i on both focal and diffuse fibrosis. At present, whether SGLT2i treatment can change the relevant indicators of myocardial fibrosis in people with diabetes and cardiovascular risk factors has not yet been reported. In addition, previous studies mainly focus on empagliflozin and dapagliflozin, and studies on canagliflozin are still very scarce. Therefore, this study intends to explore the effects of canagliflozin on myocardial fibrosis and other structures and functions of the heart in patients with type 2 diabetes mellitus and high cardiovascular risk factors.
According to the International Federation for Diabetes, diabetes now affects approximately 9.3% of the population worldwide, and the prevalence over the next two decades will continue to increase, reaching 552 million by 2030. In particular, type 2 diabetes (T2D) can cause macrovascular and microvascular complications, for example, T2D can increase the risks of ischemic stroke by 72% and stable angina by 62%. In addition, the incidence of heart failure in T2D patients is 9-22%, 2-4 times that of the general population. A significant breakthrough in contemporary cardiology was the finding that sodium-glucose-cotransporter-2 (SGLT2) inhibitors are associated with a lower risk of heart failure (HF) Hospitalization in patients with or at high risk of CV disease. In the EMPAREG OUTCOME Trial, Empagliflozin reduced cardiovascular death and hospitalisation for heart failure (HF) by 38% and 35%, respectively, with an almost immediate beneficial effect despite only a modest difference in glycaemic control, comparing two study arms over 94 weeks. The reductions in CV death were not accounted for by the reductions in atherothrombotic outcomes, as the rates of myocardial infarction and stroke remained unchanged with therapy. The proposed theory that HF is the outcome most sensitive to SGLT2 inhibition was confirmed in the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program and Dapagliflozin DECLARE-TIMI 58 trials. More recently, the EMPEROR trial showed that SGLT2 inhibition reduces the risk of hospitalisation for HF in patients regardless of the presence or absence of diabetes. The mechanisms by which SGLT2 inhibitors cause the reduction in HF risks and cardiovascular mortality are yet unknown.
Myocardial fibrosis is not only an important physiopathological mechanism of heart failure, but also has been shown to be closely associated with the risk of heart failure-related hospitalization and death, especially in patients with T2D. However, whether SGLT2i can exert cardioprotective effects by improving myocardial fibrosis remains to be further investigated. In recent years, the development of cardiac magnetic resonance (CMR) technology enables to detect focal and diffuse fibrosis in myocardial tissue, which makes it possible to systematically explore the role of SGLT2i on myocardial fibrosis.
At present, relevant studies have explored the effects of SGLT2i on cardiac structure and function. For example, there have been several related studies on left ventricular structure and function, but no consistent conclusions have been drawn: for example, the EMPA-HEART study showed that empagliflozin can reduce left ventricular mass; DAPA-HEART The LVH and SUGAR-DM-HF studies clarified the effect of dapagliflozin in reducing left ventricular mass and end-systolic volume; the REFORM study did not find that dapagliflozin had any effect on left ventricular weight. plastic effect. In addition, only the EMPA-HEART study investigated the effect of SGLT2i on both focal and diffuse fibrosis, and found that empagliflozin significantly improved diffuse fibrosis in people with diabetes and coronary heart disease. However, the SUGAR-DM-HF study did not observe changes in diffuse fibrosis with empagliflozin intervention in people with diabetes or prediabetes with reduced ejection fraction. At present, whether SGLT2i treatment can change the relevant indicators of myocardial fibrosis in people with diabetes and cardiovascular risk factors has not yet been reported. In addition, previous studies mainly focus on empagliflozin and dapagliflozin, and studies on canagliflozin are still very scarce. Therefore, this study intends to explore the effects of canagliflozin on myocardial fibrosis and other structures and functions of the heart in patients with type 2 diabetes mellitus and high cardiovascular risk factors.
9,359 studies on the registry are indexed under Diabetes Mellitus, Type 2; 1,318 are open to participants now.
This study's enrollment of 45 is below the median of 80 across 7,525 interventional studies indexed under Diabetes Mellitus, Type 2.
Browse Diabetes Mellitus, Type 2 studies →Shanghai Zhongshan Hospital is the lead sponsor of 636 studies on the registry; 283 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Those who met at leat one of the following criteria:
Exclusion Criteria:
On the basis of the original metformin medication, the experimental group took canagliflozin 1 tablet (100 mg) orally once a day (qd) before the first meal of the day, and the dosing cycle lasts 6 months.
Drug: Canagliflozin 100mg or Sitagliptin 100mg
On the basis of the original metformin medication, the experimental group took Sitagliptin 1 tablet (100 mg) orally once a day (qd) before the first meal of the day, and the dosing cycle lasts 6 months.
Drug: Canagliflozin 100mg or Sitagliptin 100mg
Eligible type 2 diabetes patients at high risks of cardiovascular diseases will be randomly assigned by a 1:1 ratio to either Canagliflozin 100 mg once daily or Sitagliptin 100 mg once daily.
Change in myocardial fibrosis
The rate of ventricular extracellular volume and late gadolinium enhancement measured by MRI
Time frame: 26 weeks since the randomization
Change in Left Ventricle (LV) Structure/Function
1. Change in left ventricle end-diastolic volume (LVEDV) and index (LVEDVI), left ventricle end-systolic volume (LVESV) and index (LVESVI), and left ventricle ejection fraction (LVEF) , measured by CMR. 2. Change in left ventricular end-diastolic/systolic diameter (LVEDD/LVESD), left ventricular ejection fraction (LVEF), interventricular septal thickness (IVS), left ventricular posterior wall thickness (LVPW), left atrial anteroposterior diameter (LA), aortic root dimension at the sinus of Valsalva (AORD), and pulmonary artery systolic pressure (PASP), measured by Echocardiography.
Time frame: 26 weeks since the randomization
Change in resting mocardial blood flow
The rate of resting myocardial blood flow (MBF, ml/min) measured by MRI
Time frame: 26 weeks since the randomization
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Plan to share: Yes — only IPD used in the results publication
Supporting information: Sap
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Shanghai Zhongshan Hospital