UBT251 Injection Phase II (Type 2 Diabetes Mellitus) Study

Exclusion Criteria

• •Known hypersensitivity to the investigational product or any of its excipients, to other GLP-1 receptor agonists, or history of clinically significant multiple or severe drug allergies; current allergic disease, high allergic disposition, or history of anaphylaxis.
• •Prior use of any of the following medications:
• •1. Any antihyperglycemic agent other than metformin within 3 months before screening, including GLP-1 analogues, oral antidiabetics, insulin, Chinese herbal medicines or health products with glucose-lowering effects.
• •2. Systemic glucocorticoids, growth hormone, or any drug that may affect glucose metabolism within 3 months before screening.
• •3. Any weight-loss medication within 3 months before screening.
• •History or evidence of any of the following conditions:
• •1. Diabetes other than type 2 (e.g., type 1 diabetes, specific types of diabetes).
• •2. Acute or chronic pancreatitis, or history of pancreatic surgery.
• •3. Symptomatic gallbladder disease within 2 years before screening (imaging-confirmed gallstones with physician-diagnosed related abdominal pain); subjects with prior cholecystectomy without sequelae may be included.
• •4. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2.
• •5. Hematologic disorders that may interfere with HbA1c measurement or increase subject risk, or any disease causing hemolysis or red-cell instability.
• •6. History of depression or severe psychiatric disorders including suicidal ideation/attempt, schizophrenia, or bipolar disorder.
• •7. Clinically significant active cardiovascular or cerebrovascular disease within 6 months before screening: myocardial infarction or unstable angina; cardiac surgery; congestive heart failure; cerebrovascular accident including stroke/TIA; any other cardiovascular/cerebrovascular condition deemed unsuitable by the investigator.
• •8. Retinopathy requiring urgent treatment at screening.
• •9. History of severe hypoglycemic coma or recurrent hypoglycemia within 2 months before randomization.
• •10. Diabetic acute metabolic complications or diabetic foot within 6 months before screening.
• •11. Gastroparesis or other disorders associated with delayed gastric emptying, uncontrolled gastro-esophageal reflux disease, or any gastrointestinal condition that, in the investigator's opinion, increases risk after study drug administration.
• •12. Major surgery, severe trauma, or severe infection within 1 month before screening judged by the investigator to preclude study participation.
• •13. History of malignancy (except adequately treated basal-cell carcinoma or carcinoma in situ of the cervix).
• •14. Concurrent medical conditions (neurologic, endocrine, psychiatric, etc.) that, in the investigator's opinion, could compromise subject safety, affect efficacy assessments, or interfere with compliance.
• •Clinically significant abnormal findings at screening, including:
• •1. Fasting C-peptide \<0.81 ng/mL.
• •2. Hepatic or renal impairment: ALT and/or AST ≥2.5×ULN; total bilirubin ≥1.5×ULN; eGFR \<60 mL·min-¹·1.73 m-².
• •3. Serum calcitonin ≥50 pg/mL.
• •4. Unstable thyroid medication requirement or clinically significant abnormal thyroid function tests necessitating new treatment.
• •5. Fasting triglycerides ≥5.6 mmol/L.
• •6. Serum amylase and/or lipase \>2.0×ULN.
• •7. INR above the upper limit of normal.
• •8. Hemoglobin \<110 g/L (males) or \<100 g/L (females).
• •9. Uncontrolled or untreated hypertension.
• •10. Clinically significant ECG abnormalities: second- or third-degree AV block; long-QT syndrome or QTcF \>470 ms (female) or \>450 ms (male); pre-excitation syndrome; or any severe arrhythmia requiring treatment.
• •11. Any physical examination, vital sign, or laboratory abnormality that, in the investigator's judgment, poses significant risk to the subject or may interfere with safety, PK, or PD evaluations.
• •Positive tests for:
• •* HBsAg with HBV DNA above the reference range;
• •* Anti-HCV with HCV RNA above the ULN;
• •* HIV antibody;
• •* Treponemal antibody (syphilis).
• •Blood loss or donation \>400 mL, or receipt of blood/blood products within 3 months before screening; hemoglobinopathy, hemolytic anemia, or sickle-cell disease.
• •Participation in another clinical trial within 3 months before screening.
• •History of alcohol or drug abuse; alcohol abuse defined as \>14 standard drinks per week (men) or \>7 (women).
• •Pregnant or lactating women.
• •Inability to tolerate venipuncture, or history of vasovagal syncope or severe needle phobia.
• •Any other condition that, in the investigator's opinion, renders the subject unsuitable for the trial.