Exclusion criteria:
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(1) Excessive alcohol consumption for 3 months or more in the first year before screening (on average, men drank more than 30 grams of alcohol every day, which is equivalent to 3.75 units of alcohol, and women drank more than 20 grams, which is equivalent to 2.5 units of alcohol: 1 unit=285 mL of beer, or 25 mL of spirits, or 100 mL of wine);
(2) Liver and biliary diseases suspected to have other causes through medical history and laboratory tests, including but not limited to: hepatitis B or C virus infection, alcoholic liver disease, drug-induced liver disease, autoimmune hepatitis, cirrhosis, primary sclerosing cholangitis, Wilson's disease,α 1 - antitrypsin deficiency, liver cancer (or family history of liver cancer), etc;
(3) In the year before screening, there was more than 2 weeks of medication history (amiodarone, methotrexate, systemic glucocorticoid, tetracycline, tamoxifen, estrogen greater than hormone replacement dose, synthetic steroids, valproic acid and other known liver toxins) that could cause hepatic steatosis or steatohepatitis;
(4) Liver protecting drugs (including but not limited to reduced glutathione, glucurolactone, glycyrrhizic acid preparation, nicotinamide, diphenyl diester, liver protecting tablets, silymarin (guest), polyene phosphatidylcholine, S-adenosylmethionine, ursodeoxycholic acid, vitamin E and other Chinese herbs that affect liver function) were used within 4 weeks before enrollment;
(5)(5) At the time of randomization or in the past, patients suffered from ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis or liver transplantation, or planned liver transplantation;
(6) Type 1 diabetes;
(7) Patients with type 2 diabetes were treated with hypoglycemic drugs (except GLP-1 receptor agonist and pioglitazone) before randomization, and the dose was stable for less than 3 months;
(8) Receive GLP-1 receptor agonist and pioglitazone treatment within 90 days before enrollment (those who stop taking the drug more than 3 months before enrollment can be included);
(9) The blood pressure was not well controlled (≥ 160/100mmHg) with stable dose of antihypertensive drugs within 3 months before randomization;
(10) The blood lipid is abnormal, and the use of lipid-lowering drugs is unstable within 3 months before randomization (such as statins, beta drugs, niacin, coelenamine, high-purity fish oil preparations, etc.);
(11) Model for End-stage Liver Disease (MELD) score>12, or Child Turcotte Pugh (CTP) score>6;
(12) Patients who received vitamin E (dose ≥ 300mg/day), obenzoic acid, berberine and other drugs to treat NASH for more than 1 year, or received vitamin E (dose ≥ 300mg/day), obenzoic acid, berberine and other drugs to treat NASH within 90 days before enrollment (those who stopped taking drugs within 1 year and more than 3 months before enrollment can be selected);
(13) Have a history of weight loss surgery or plan to perform weight loss surgery (within 1 year);
(14) Body weight was unstable within 3 months before randomization (increase or decrease>5%); Use any drug with definite weight loss/weight loss effect within 3 months before randomization, such as orlistat, liraglutide, fentamine, topiramate, chlorocarselin hydrochloride, naltrexone hydrochloride, diethylamine phenylacetone, benzotriazine tartrate, etc;
(15) Myocardial infarction and unstable angina occurred within 6 months before screening, or coronary intervention (diagnostic angiography is allowed) or vascular transplantation was performed within 6 months, or New York Heart Function Classification (NYHA) III or above;
(16) Complicated with serious blood system (various severe anemia, hemophilia, etc.), kidney disease (chronic kidney disease, renal insufficiency, etc.), respiratory system (active pulmonary tuberculosis, severe pulmonary infection, etc.), digestive system (active gastrointestinal ulcer, refractory colitis, etc.), nervous system and other primary diseases and psychosis (including a history of mental illness or a family history of mental illness)
(17) History of chronic or acute pancreatitis or serum lipase/amylase elevation>2 times ULN or fasting serum triglyceride level>500 mg/dL (>5.65 mmol/L) during screening (if it is judged by the investigator to be a transient increase caused by diet, a reexamination is allowed within 7 days), or hypothyroidism;
(18) Complications of diabetes, known peripheral vascular diseases or clinically significant neuropathy that may increase the risk of amputation;
(19) Being treated with anticoagulant drugs (such as warfarin, heparin, etc.)
(20) The following laboratory inspection exceptions exist:
eGFR<60 mL/min/1.73m2 [Calculation formula: Ccr: (140-age) × Weight (kg)/(0.818 × Scr( μ Mol/L), female × 0.85
Platelet count<lower limit of normal reference value;
Bilirubin level>1.5 times ULN (known Gilbert disease with conjugated bilirubin<0.3 mg/dL (<5.13 μ Mol/L));
International normalized ratio (INR) ≥ 1.3 (if laboratory error is suspected, a recheck is allowed);
ALT and/or AST>5 times ULN, or ALP ≥ 2 times ULN (if the elevation of ALP is not from the liver, it can be considered to be included in the group) (reexamination is allowed within 7 days);
Glycosylated hemoglobin (HbA1c)>8.5%;
AFP>upper limit of normal reference value (one recheck is allowed);
(21) There are MRI scanning contraindications, including but not limited to: severe claustrophobia, inner ear implants, pacemakers or other implanted rhythm management equipment, intracranial aneurysm clips incompatible with MRI, any other metal, non MRI compatible implant equipment (such as insulin pump, hip replacement), medical history of orbital metal fragments that have not been removed, weight or waist circumference that exceeds the scanner function, etc;
(22) HIV infection positive;
(23) Allergy to the test drug or its components, or a history of severe allergy;
(24) Pregnant or lactating women, fertile subjects are unwilling or unable to take effective contraceptive measures within 6 months from the screening period to the termination of taking the trial drug;
(25) Participated in other intervention clinical trials within 12 weeks before screening;
(26) The researcher believes that there are other circumstances that are not suitable for this study.
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