Efficacy and Safety Comparison of Cofrogliptin Add-on Versus Metformin Dose-escalation in Type 2 Diabetes Patients Inadequately Controlled With SGLT-2 Inhibitors Plus Low-Dose Metformin:A Multicenter, Open-Label Trial

Exclusion Criteria

• •Type 1 diabetes mellitus.
• •Various types of secondary diabetes.
• •Pending or having undergone pancreatic or β-cell transplantation.
• •History of pancreatitis or pancreatic resection.
• •Complicated with diabetic ketoacidosis or hyperosmolar coma.
• •Moderate or severe liver insufficiency of any cause, defined as ALT (SGPT), AST (SGOT), or alkaline phosphatase serum levels greater than 3 times the upper limit of normal (ULN) during the screening period.
• •Acute coronary syndrome (ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, unstable angina), stroke, or transient ischemic attack (TIA) within the past 3 months.
• •Uncontrolled hypertension: systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 90 mmHg.
• •Hemoglobin level less than 10 g/l or 100 mg/dl.
• •Recurrent genitourinary infections more than twice within the past 3 months.
• •History of bariatric surgery or other gastrointestinal surgeries causing chronic malabsorption within the past 2 years.
• •Received anti-obesity medication within the past 3 months or any other treatment (e.g., surgery, radical diet plans) that led to unstable body weight at the time of screening.
• •History of cancer (except basal cell carcinoma) and/or cancer treatment within the past 5 years.
• •Human immunodeficiency virus (HIV) positivity.
• •Severe peripheral vascular disease.
• •Hematological malignancies or any diseases causing hemolysis or erythrocyte instability (e.g., malaria, babesiosis, hemolytic anemia).
• •Coexisting immune system diseases or currently receiving systemic corticosteroid therapy.
• •Changes in thyroid hormone dosage within the past 6 weeks, or any other uncontrolled endocrine or metabolic disorders outside of T2DM.
• •Alcohol or drug abuse within the past 3 months that may reduce trial compliance, or any chronic illnesses that the investigator believes may lead to reduced trial compliance or reduced use of the study drug.
• •Known allergies to components of the study medication or other drugs with similar chemical structures or excipients.
• •Pregnant women, women planning to become pregnant during the study, or lactating women. Subjects unwilling to use reliable contraception (including condoms, spermicides, or intrauterine devices) from the time of signing the informed consent form until 28 days after the last administration of the study medication, or women planning to use progesterone-containing contraceptives during this period. Men with fertility plans during the study.
• •Participation in any other clinical study within the past 30 days.
• •Any other condition deemed unsuitable for participation in this study by the investigator.