Canagliflozin and Myocardial Fibrosis (CANA-DIA-FIB)

December 8, 2025 updated by: Shanghai Zhongshan Hospital

Canagliflozin Attenuates CMR-Quantified Myocardial Fibrosis in Patients With Type 2 Diabetes Mellitus at High Cardiovascular Risk

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200000
        • Zhongshan Hospital, Fudan University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • History of type 2 diabetes;
  • Haemoglobin A1c ≥7.0% and < 10.5%;
  • Patients who have received a stable dose of metformin or metformin combined with insulin secretagogues and/or insulin therapy for 4 weeks before enrollment;

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

    1. Patients with at least 3 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 or 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Canagliflozin group
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
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.
Placebo Comparator: Sitagliptin group
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in myocardial fibrosis
Time Frame: 26 weeks since the randomization
The rate of ventricular extracellular volume and late gadolinium enhancement measured by MRI
26 weeks since the randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Left Ventricle (LV) Structure/Function
Time Frame: 26 weeks since the randomization
  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.
26 weeks since the randomization
Change in resting mocardial blood flow
Time Frame: 26 weeks since the randomization
The rate of resting myocardial blood flow (MBF, ml/min) measured by MRI
26 weeks since the randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Zhongshan Hospital

Investigators

  • Principal Investigator: Xiaoying Li, PhD, Fudan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 5, 2022

Primary Completion (Actual)

December 31, 2024

Study Completion (Actual)

March 20, 2025

Study Registration Dates

First Submitted

December 7, 2021

First Submitted That Met QC Criteria

May 4, 2022

First Posted (Actual)

May 10, 2022

Study Record Updates

Last Update Posted (Estimated)

December 16, 2025

Last Update Submitted That Met QC Criteria

December 8, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZSE-202112

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

only IPD used in the results publication

IPD Sharing Time Frame

No time limited.

IPD Sharing Access Criteria

Anyone can access the Statistical Analysis Plan (SAP).

IPD Sharing Supporting Information Type

  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Type 2 Diabetes

Clinical Trials on Canagliflozin 100mg or Sitagliptin 100mg

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Angola

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe