Canagliflozin and Myocardial Micro-perfusion

• Status: Recruiting
• Trial end date: 2023-06-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Shanghai Zhongshan Hospital
• Treatments: Canagliflozin; Sitagliptin Phosphate

Criteria

Inclusion Criteria:

• History of type 2 diabetes;

• Haemoglobin A1C ≥6.5 and ≤10 %;

• Patients who have received a stable dose of metformin for 4 weeks before enrollment;

• Those who met at leat one of the following criteria:

1. Patients with type 2 diabetes duration ≥ 10 years and with at leat 2 of the folllowing risk factors: (1) male >55 years old, or female > 65 years old; (2) ； BMI≥25 kg/m2; (3) hypertension; (4) dyslipidemia; (5) current smoker (Brinkman index ≥ 200;

2. Any of the following signs of target organ damage are present: (1) albuminuria (ACR≥300mg/g); (2) 45 ml/min/1.73 m2 ≤eGFR<90 ml/ min/1.73 m2; (3) Left ventricular hypertrophy coupled with retinopathy.

Exclusion Criteria:

• Female subjects who are pregnant, lactating or of child bearing potential, or pre-menopausal women. (Menopause will be determined by patient and physician history;

• Subjects currently treated with SGLT2 inhibitors, GLP1 receptor agonist, or sitagliptin;

• Significant allergy or known intolerance to Canagliflozin or Sitagliptin;

• History of hypovolemia, amputation, peripheral vascular disease, diabetic foot ulcers;

• History of diagnosed cardiovascular diseases, including myocardial infarction, hospitalization for unstable angina pectoris, cerebral infarction (ischemic stroke), coronary artery bypass grafting, percutaneous coronary intervention (with or without stents) Implantation), peripheral vascular reconstruction (angioplasty or surgery), heart failure, arrhythmia, heart valve disease;

• AST or ALT ≥ 3 times the upper limit of normal;

• eGFR <45 ml/min/1.73 m2；

• type 1 diabetes;

• Diabetic ketosis or diabetic hyperosmolar coma;

• History of respiratory disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension, etc.);

• Existing hypertensive emergency (systolic/diastolic blood pressure exceeding 180/120mmHg) at the time of enrollment, or evaluated For refractory hypertension (after the use of sufficient doses of 3 antihypertensive drugs, the systolic blood pressure is still> 140 or Diastolic blood pressure> 90mmHg);

• Known impaired gastrointestinal function or gastrointestinal diseases that may significantly affect the absorption of the test drug, such as: diagnosed active ulcers (Forrest grade II and below), inflammatory bowel disease, malabsorption related diseases, and non-absorbent diseases. Controlled diarrhea, gastrointestinal surgery (such as bariatric surgery);

• Patients with diagnosed malignant tumors;

• Participate in other clinical trials within 3 months;

• Other creteria that were not eligible to participate in the clinical trial.