The Effect of Henagliflozin and Metformin on Myocardial Tissue-level Characteristics

Study Overview
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Brief Summary
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This is a prospective, randomized, open-label, active drug controlled clinical trial that aims to compare the effects of henagliflozin or metformin on myocardial tissue level characteristics in type 2 diabetes patients with obesity. Eligible subjects with type 2 diabetes before randomisation and fulfilling all of the inclusion criteria and none of the exclusion criteria will be randomised in a 1:1 ratio to henagliflozin 10 mg once a day or metformin 1000 mg twice a day and treated for 24 weeks. The study includes five visits.

Detailed Description
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MRI scanning will be assessed at baseline and at the end of the treatment period in order to to assess the cardiac morphology, cardiac function, and myocardial tissue characteristics. The cardiac MRI examination will be performed in accordance with a pre-defined MRI protocol. Images from all sites will be analyzed centrally at the core-lab using a dedicated software package and certified analysts.

Official Title
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The Effect of Henagliflozin and Metformin on Myocardial Tissue-level Characteristics in Patients With Type 2 Diabetes and Obesity: A Prospective, Randomized, Open-label, Active Drug Controlled Clinical Trial

Conditions
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Obesity, Type 2 Diabetes, Sodium-glucose Co-transporter-2 Inhibitor, Myocardial Fibrosis, Magnetic Resonance Imaging

Intervention / Treatment
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* Drug: Henagliflozin
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals with type 2 diabetes newly diagnosed based on the WHO (1999) criteria; Hemoglobin A1c levels >=7.0% and <=8.0%; Females or males ≥18 years up to 75 years of age. Exclusion Criteria: Females or males <18 years. Clinical diagnosis of type 1 diabetes and other types of diabetes. Blood pressure at screening that would require a change in blood pressure treatment over the study period. History of stroke or other clinically significant cerebrovascular disease. Any of the following cardiovascular diseases: Atrial fibrillation, or other unstable or severe arrhythmia affecting heart function Unstable heart failure or any heart failure with NYHA class III and IV Significant valvular disease Significant peripheral artery disease Active malignancy requiring treatment at the time of visit 0. Patients with severe hepatic impairment. Unstable or rapidly progressing renal disease. Ongoing treatment with loop diuretics. Estimated Glomerular Filtration Rate (eGFR) <45 mL/min/1.73 m2. Women who has a positive pregnancy test at enrolment or randomization, or are breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Henagliflozin<br>Henagliflozin 10mg qd po | Drug: Henagliflozin<br>* Henagliflozin 10mg qd po<br>* Other names: SHR3824;|
| Active Comparator: Metformin<br>Metformin 1000mg bid po | Drug: Metformin<br>* Metformin 1000mg bid po<br>* Other names: Metformin Hydrochloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extra-cellular volume fraction | To compare the effects of henagliflozin and metformin on extra-cellular volume fraction | baseline and week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in HbA1c Levels | To compare the effects of henagliflozin and metformin on HbA1c Levels | baseline and week 24 | 
| Mean change in body mass index | To compare the effects of henagliflozin and metformin on body mass index | baseline and week 24 | 
| Mean change in blood pressure | To compare the effects of henagliflozin and metformin on blood pressure | baseline and week 24 | 
| Mean change in level of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | To compare the effects of henagliflozin and metformin on level of Homeostatic Model Assessment of Insulin Resistance | baseline and week 24 | 
| Native T2 mapping | To compare the effects of henagliflozin and metformin on native T2 mapping | baseline and week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metformin