A Study of TG103 Injection Combined With Metformin in Treatment of Type 2 Diabetes Mellitus

Inclusion criteria

• Subjects have diagnosed with type 2 diabetes according to the Guidelines for prevention and treatment of type 2 diabetes in China (2020 Edition), T2DM was diagnosed at least 8 weeks before screening;
• Aged 18 to 75 years (inclusive), no gender limitation;
• Body Mass Index (BMI): 18.5≤BMI≤40;
• Received stable dose of metformin hydrochloride monotherapy for ≥8 weeks before screening and metformin dose ≥1500 mg/ day ;
• HbA1c must meet the following criteria:

• Screening: 7.5% ≤ HbA1c ≤ 11.0% (Local laboratory)
• Baseline: 7.0% ≤ HbA1c ≤ 10.5% (Central laboratory)
• Subjects of childbearing potential must use reliable methods of contraception throughout the study period and at least 3 months after the last dose to avoid pregnancy in female subjects or pregnancy in the male subject's partner;
• Willing and able to accurately use home glucose meter for self-glucose monitoring;
• Be able to understand and follow the trial procedure, voluntarily participate in the trial and sign the informed consent form.

Exclusion criteria

• Type 1 diabetes;
• Body weight change more than 5% within 1 month prior to screening;
• Received any of the following medications:

• Prior discontinuation of DPP-4 inhibitors or GLP-1 receptor agonists for efficacy, tolerability, and safety reasons;
• Systemic glucocorticoid and growth hormone,or other drugs affecting glucose metabolism have been used within 8 weeks before screening;
• History of ≥2 episodes of grade 3 hypoglycemia within 6 months prior to screening, or grade 3 hypoglycemia between screening to randomization;
• Acute complications of diabetes, such as diabetic ketoacidosis and hyperglycemic hyperosmolar status, occurred ≥1 time within 6 months prior to screening;
• Severe chronic complications of diabetes (e.g., proliferative diabetic retinopathy, severe diabetic neuropathy, diabetic foot, etc.) within 6 months prior to screening
• History of acute or chronic pancreatitis prior to screening;
• Subjects with clinically significant gastric emptying abnormalities (e.g., gastric outlet obstruction), severe chronic gastrointestinal diseases (e.g., gastroparesis, inflammatory bowel disease, or intestinal obstruction) within 6 months prior to screening, or who have undergone gastrointestinal surgery that affects gastric emptying;
• Any of the following cardiovascular events within 6 months prior to screening: decompensated cardiac insufficiency (NYHA class III or IV); history of unstable angina pectoris, myocardial infarction, coronary artery bypass grafting, or coronary stent implantation; or long QT syndrome or prolonged QTcF interval (QTcF: male >450 ms, female >470 ms) on 12-lead ECG; severe arrhythmias that are evaluated by the investigator to be inappropriate for participation in this clinical trial;
• Hemorrhagic stroke or acute ischemic stroke disease occurred within 6 months prior to screening;
• History of psychiatric diseases (such as depression, anxiety, etc.) during screening; or symptomatic gallbladder disease; or history of other diseases that may endanger the safety of the subject and that the investigator deems inappropriate for enrollment;
• Any type of malignant tumor treated or untreated within 5 years prior to screening (except for clinically cured basal cell carcinoma or carcinoma in situ);
• Severe infection within 4 weeks prior to screening, or refractory urinary tract or genital infection within 6 months prior to screening;
• Having a significant blood system disease (e.g., aplastic anemia, myelodysplastic syndrome) or any disease causing hemolysis or red blood cell instability (e.g., malaria) at screening;
• Subjects with thyroid dysfunction that cannot be controlled by a stable drug dose at screening, or with clinically significant abnormalities in thyroid function examination results requiring drug treatment at screening;
• Personal or family history of medullary thyroid cancer (MTC) or type 2 multiple endocrine tumor syndrome at screening;
• Any of the indicators meet the following criteria:

• i. Systolic blood pressure ≥ 160mmHg or diastolic blood pressure ≥ 100mmHg at screening or before randomization;
• ii. Laboratory tests show any of the following abnormalities:

• FPG≥13.9 mmol/L;
• ALT or AST≥2.5×ULN;
• Total bilirubin (TBiL) ≥2.0×ULN;
• Triglyceride >5.7 mmol/L;
• eGFR<45 mL/(min*1.73 m^2);
• Serum amylase and/or lipase ≥3×ULN;
• Hemoglobin <100 g/L;
• Calcitonin≥50 ng/L(pg/mL);
• iii. Serological examination:

• Human immunodeficiency virus antibody or treponema pallidum antibody is positive;
• Hepatitis C antibody is positive, and HCV RNA was higher than the lower limit of the detection reference range;
• Hepatitis B surface antigen is positive, and the quantitative detection result of HBV DNA was higher than the lower limit of the detection reference range;
• Known allergy to the test drug, Dulaglutide, Empagliflozin, or related excipients;
• Subjects who have lost more than 400 mL blood due to blood donation or other reasons within 3 months prior to screening;
• Average alcohol intake more than 21 units of alcohol (male)/14 units of alcohol (female) per week within the 3 months prior to screening (1 unit ≈360 mL beer, or 45 mL spirits with 40% alcohol content, or 150 mL wine);
• Subject participated in any drug or medical device clinical study within 3 months prior to screening (except for screening failure);
• Pregnant or lactating female;
• Not suitable for this study in the investigator's opinion.