Efficacy, Safety, and Tolerability of CS0159 Combined With Semaglutide in MAFLD Patients With Obesity and T2DM

Inclusion Criteria:

• 1. Age≥18 and ≤65 years, male or female.
• 2. MRI-PDFF ≥10% within 3 months prior to randomized.
• 3. Diagnosis of T2DM.
• 4. HbA1c: 7.0%-10.5%.
• 5. FPG: 7.0-13.3 mmol/L.
• 6. BMI: 30-45 kg/m2.
• 7. Subjects control blood glucose only by lifestyle intervention for at least 3 months before the screening period.
• 8. Willing to maintain consistent diet and exercise habits throughout the entire study, and adhere to the study protocol for timely administration of the study drug, and timely self-monitoring of blood glucose and recording.
• 9. Can understand the research content, follow the research protocol, and voluntarily sign the ICF.

Exclusion Criteria:

• 1. ALT≥2.5×ULN, AST≥2.5×ULN, TBil≥2×ULN, creatinine (Cr) ≥1.5×ULN and Serum creatinine clearance<60 mL/min, PLT<100×10^9/L, INR >1.3, ALB <3.5 g/dL.
• 2. Use of glucose-lowering medication in the 3 months prior to randomization.
• 3. Weight loss ≥ 5% in the 3 months prior to randomization or ≥10% in the 6 months prior to randomization or use of other weight-lowering drugs, corticosteroids, and etc.
• 4. History of allergy to glucagon-like peptide-1 receptor agonists (GLP-1RA) medications, currently in an allergic state, having allergic conditions, or history of allergies to ≥2 substances.
• 5. Subjects with T1DM, monogenic diabetes, diabetes caused by pancreatic damage, or other secondary diabetes.
• 6. Subjects with a history of severe pruritus.
• 7. Uncontrolled and potentially unstable diabetic retinopathy or maculopathy.
• 8. Thyroid C-cell tumour or family history, multiple endocrine neoplasia type 2 or family history.
• 9. History of acute or chronic pancreatitis.
• 10. Subjects with Child-Pugh class B or C grade cirrhosis.
• 11. HBsAg positive, HCV Ab positive, HIV Ab positive, TP Ab positive.
• 12. Arrhythmias, male QTc≥450 ms, or female QTc≥470 ms. Or cardiovascular disease for which the researcher has assessed that participation in the trial is not appropriate.
• 13. Diseases that interfere with the absorption, distribution, metabolism or excretion.
• 14. Gastrointestinal diseases that affect food digestion and absorption.
• 15. Use moderate or strong inhibitors or inducers of cytochrome P450 enzyme (CYP3A4 enzyme) within the first 14 days of randomization and throughout the entire trial period.
• 16. History of malignant tumors within the first 5 years of randomization.
• 17. Serious hypoglycemic events occurring ≥ 3 times within 12 weeks prior to administration, or acute and severe metabolic disorder occurred within 12 weeks prior to administration.
• 18. Drug abuse or alcohol abuse within the first 6 months of randomization.
• 19. Poor blood pressure control.
• 20. Mental illness, epilepsy.
• 21. Patients with uncontrollable severe infectious diseases before randomization.
• 22. Pregnant, planned pregnancy or breastfeeding.
• 23. Participated in other clinical trials in the first three months of randomization.
• 24. Any condition that in the judgement of the researcher precludes participation.