Effect of Henagliflozein on Hepatic Fat Content in Patients With T2DM and NAFLD

Inclusion criteria

• Patients diagnosed with type 2 diabetes within 5 years (According to the diagnostic criteria of WHO Diabetes Classification 2019)
• Patients who are aware of the purpose of the trail, willing to participate in the trial and sign informed consent forms, and comply with all requirements (including those during follow-up and evaluation investigations)
• Well-controlled blood glucose through diet and exercise intervention, or stable treatment with 1 or 2 types of hypoglycemic drugs (metformin, sulfonylurea, glinide, α-glycosidase inhibitor ) for at least 8 weeks with a half or full recommended maximum tolerated dose in instructions.
• HbA1c: 7.0%-8.5%
• Patients diagnosed with non-alcoholic fatty liver disease (According to the diagnostic criteria of Guidelines for Diagnosis and Treatment of Non-alcoholic Fatty Liver Disease 2010)

Exclusion criteria

• Patients with type 1 diabetes, gestational diabetes or other special types of diabetes;
• Patients with any acute, chronic complication or risk that may cause greater adverse effects than benefits through the trial; or receiving other treatment currently that may affect subjects' compliance or the objectivity of the end point of this trial; (1)Patients with serious acute complications of diabetes in the past 6 months (Eg. diabetic ketoacidosis, hyperosmotic hyperglycemia coma); (2)Patients with unstable proliferative retinopathy or maculopathy,severe diabetic neuropathy, intermittent claudication or diabetic foot in the past 6 months; (3)Patients with serious liver dysfunction and chronic kidney disease or disease of other systems (Eg. Acute and chronic pancreatitis, liver cirrhosis, nephrotic syndrome ect. ); and those who do not meet the requirements after being evaluated by professionals; (4)Have a history of myocardial infarction, unstable angina pectoris, stroke or transient ischemic attack, or underwent coronary angioplasty, percutaneous coronary stenting or coronary artery bypass grafting 6 months before the screening; or screening for congestive heart failure (New York Heart Association NYHA grade III and IV), unstable or acute congestive heart failure, or persistent arrhythmias believed to be life-threatening within the first 6 months of the trail; (5)Have a history of hemorrhagic stroke or ischemic stroke in the past 6 months, and was evaluated by the researchers as not suitable to participate in this clinical trial; (6)Have a history of hypertension and was not effectively controlled before screening: systolic blood pressure (SBP) ≥ 160mmHg and / or diastolic blood pressure (DBP) ≥ 100mmHg;
• Have a history of other endocrine system diseases which affect glucose and lipid metabolism or have an effect on the body weight, such as: multiple endocrine adenomatosis, acromegaly, Cushing syndrome, hyperthyroidism;
• Have a history of malignant tumour within 5 years before screening, except for local basal cell carcinoma of the skin after treatment；
• Have a history of severe infection, trauma or major surgery within 3 months;
• Have a history of drug abuse with 5 years, including repeated use of dependence-producing drug unrelated to medical purposes, including addictive and habitual drugs leading to physical and psychic dependence;
• Have a history of participating any intervention drug or instrumental clinical trial 3 months before screening;
• Have a history of severe anemia or need regular blood transfusion treatment;
• Have a history of any medication or treatment below:

(1)Using drugs that may cause weight change 90 days before screening, including diuretics, weight-loss drug etc.; (2)Using drugs that may affect blood glucose for >1 week within 12 weeks, such as oral/intravenous glucocorticoid, growth hormone, estrogen/progesterone, high-dose diuretics, antipsychotic drugs, etc., but low-dose diuretics for antihypertensive purposes (hydrochlorothiazide < 25mg/d, indapamide < 1.5 mg/d) are not included in this restriction; (3)Had bariatric sugery or planning to have bariatric surgery; 10.The laboratory results of patients meet the following standards:

• AlanineAminotransferase(ALT)and/oraspartateaminotransferase(AST) higher than 5 times of the upper limit of the normal value.
• Glomerular Filtration Rate (eGFR) estimated by CKD-EPI formula < 40mL/ (min·1.73m2); 11.Patients are currently pregnant, breastfeeding or planning a pregnancy; 12.Have a history of infectious diseases such as hepatitis B (HBs-Ag), hepatitis C (HCV-Ab), pulmonary tuberculosis or sexually transmitted active diseases such as HIV and syphilis; 13.Have a history of using anti-NASH drugs (vitamin E, ursodeoxycholic acid, s-Adenosylmethionine, betaine, silymarin, gemdibrozil, anti-TNF therapy, probiotics, ect.) within 3 months before random grouping; 14.Having structural and functional genitourinary abnormalities prone to cause genitourinary infection; 15.Patients with abnormal hematologic system or any diseases that may cause hemolysis or unstable erythrocyte; 16.Have a history of using immunomodulators, such as biological agents, cyclophosphamide, cyclosporine, etc.; 17.Patients with MRI incompatible metal or magnetic implant, device or materials.