Overview

This is a randomized, double-blind, placebo- and active-controlled, multicenter Phase II clinical trial designed to evaluate the efficacy, safety, and pharmacokinetic characteristics of MWN109 tablets in participants with type 2 diabetes mellitus (T2DM).

Eligible participants will be randomized to receive different dose levels of MWN109 tablets, MWN109-matched placebo, or semaglutide tablets 14 mg (active control), administered once daily for 20 consecutive weeks.

Approximately 240 adults aged 18 to 75 years with type 2 diabetes mellitus will be enrolled. The primary endpoint is the percent change from baseline in HbA1c at Week 20. Secondary endpoints include glycemic parameters, body weight, metabolic parameters, adverse events, and immunogenicity.

Eligibility

Inclusion Criteria:

1. Male or female participants aged 18 to 75 years (inclusive) at the time of signing the informed consent form.
2. Diagnosis of type 2 diabetes mellitus for at least 3 months prior to screening, with inadequate glycemic control despite treatment with lifestyle intervention or a stable dose of metformin monotherapy (≥1500 mg/day, or ≥1000 mg/day if at the maximum tolerated dose) for at least 3 months prior to screening.
3. HbA1c ≥7.5% and ≤11.0% at screening and before randomization (central laboratory).
4. Fasting plasma glucose ≤13.9 mmol/L at screening and before randomization (central laboratory; may be re-tested once within 1 week if special circumstances apply).
5. BMI ≥20.0 kg/m² and ≤40.0 kg/m² at screening.
6. Self-reported body weight change of \<5% during the at least 12 weeks prior to screening.

Exclusion Criteria:

1. Known allergic constitution (allergy to 3 or more foods or drugs), allergy to GLP-1 receptor agonists or any component of the study drug, severe allergic disease, or a history of severe drug allergy.
2. Diagnosed or suspected type 1 diabetes mellitus, other specific types of diabetes mellitus (excluding gestational diabetes mellitus), or secondary diabetes mellitus.
3. Severe chronic complications of diabetes mellitus (e.g., diabetic nephropathy, proliferative diabetic retinopathy, non-proliferative diabetic retinopathy requiring treatment, peripheral vascular disease with amputation, chronic foot ulcer, intermittent claudication, or painful diabetic neuropathy).
4. Use of insulin within 1 year prior to randomization (except for acute short-term use of ≤14 days).
5. Diabetic ketoacidosis or hyperosmolar hyperglycemic state within 24 weeks prior to randomization.
6. Grade 3 hypoglycemia within 12 months prior to randomization, or ≥3 episodes of Grade 2 hypoglycemia or hypoglycemia-related symptoms within 3 months prior to screening.
7. Trauma, infection, or surgery within 12 weeks prior to randomization that significantly affects glycemic control, or planned surgery during the study period (excluding outpatient procedures).
8. Blood transfusion or blood donation/blood loss ≥400 mL within 12 weeks prior to randomization, or ≥200 mL within 4 weeks prior to screening, or hematologic diseases that may affect HbA1c or pose a safety risk.
9. Any unstable or untreated endocrine disease other than type 2 diabetes mellitus (e.g., multiple endocrine neoplasia, acromegaly, Cushing's syndrome).
10. History of thyroid disease (except under specific circumstances) or abnormal TSH (TSH \>6.0 or \<0.4 mIU/L in participants without a history of thyroid disease).
11. Medullary thyroid carcinoma, multiple endocrine neoplasia type 2 (MEN2), or a personal or first-degree family history of these conditions.
12. Significant active autoimmune abnormalities (e.g., systemic lupus erythematosus, rheumatoid arthritis) requiring systemic glucocorticoids.
13. Major cardiovascular or cerebrovascular diseases within 24 weeks prior to screening or before randomization (e.g., myocardial infarction, cerebrovascular accident, unstable angina).
14. Known or pre-randomization ECG abnormalities with significant safety risk (e.g., QTcF \>450 ms).
15. History of sporadic or frequent premature beats or tachycardia, or heart rate \>100 beats/min before randomization.
16. Uncontrolled hypertension at screening or before randomization (≥160/100 mmHg) or untreated hypertension meeting this criterion.
17. Clinically significant abnormal laboratory findings at screening or before randomization (e.g., ALT or AST ≥3×ULN, eGFR \<60 mL/min/1.73 m², anemia, calcitonin ≥35 ng/L).