UBT251 Injection Phase II (Type 2 Diabetes Mellitus) Study

Prior treatment

• 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.
• 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.

Other illness

• History of alcohol or drug abuse; alcohol abuse defined as \>14 standard drinks per week (men) or \>7 (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.

Lab values

• Prior use of any of the following medications:
  • 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.
  • Systemic glucocorticoids, growth hormone, or any drug that may affect glucose metabolism within 3 months before screening.
  • Any weight-loss medication within 3 months before screening.
• History or evidence of any of the following conditions:
  • Diabetes other than type 2 (e.g., type 1 diabetes, specific types of diabetes).
  • Acute or chronic pancreatitis, or history of pancreatic surgery.
  • 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.
  • Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2.
  • Hematologic disorders that may interfere with HbA1c measurement or increase subject risk, or any disease causing hemolysis or red-cell instability.
  • History of depression or severe psychiatric disorders including suicidal ideation/attempt, schizophrenia, or bipolar disorder.
  • 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.
  • Retinopathy requiring urgent treatment at screening.
  • History of severe hypoglycemic coma or recurrent hypoglycemia within 2 months before randomization.
  • Diabetic acute metabolic complications or diabetic foot within 6 months before screening.
  • 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.
  • Major surgery, severe trauma, or severe infection within 1 month before screening judged by the investigator to preclude study participation.
  • History of malignancy (except adequately treated basal-cell carcinoma or carcinoma in situ of the cervix).
  • 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:
  • Fasting C-peptide \<0.81 ng/mL.
  • 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.
  • Serum calcitonin ≥50 pg/mL.
  • Unstable thyroid medication requirement or clinically significant abnormal thyroid function tests necessitating new treatment.
  • Fasting triglycerides ≥5.6 mmol/L.
  • Serum amylase and/or lipase \>2.0×ULN.
  • INR above the upper limit of normal.
  • Hemoglobin \<110 g/L (males) or \<100 g/L (females).
  • Uncontrolled or untreated hypertension.
  • 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.
  • 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).

Other

• Pregnant or lactating women.

• Age 18-75 years (inclusive) at the time of informed consent; sex not restricted.
• Documented diagnosis of type 2 diabetes mellitus with HbA1c ≥7.0% and ≤10.5% at screening.
• Lifestyle intervention or stable-dose metformin treatment (≥1000 mg/day) for at least 3 months before screening; "stable" defined as no change in daily dose during this period.
• Body weight: ≥50.0 kg for men and ≥45.0 kg for women at screening; body-mass index (BMI) 23.0-40.0 kg/m² (inclusive).
• Subject (and partner) agrees to use effective contraception from screening until 6 months after study completion and has no plans to donate sperm or ova during this period.
• Has been fully informed about the study and voluntarily signed the written informed consent form.