To Evaluate the Efficacy and Safety of Initial Combination Therapy With DWP16001 and DWC202518 Compared to DWP16001 Monotherapy and DWC202518 Monotherapy in Patients With Type 2 Diabetes Mellitus

A Multicenter, Randomized, Double-Blind, Active-Controlled, Parallel-Group, Phase III Study to Evaluate the Efficacy and Safety of Initial Combination Therapy With DWP16001 and DWC202518 Compared to DWP16001 Monotherapy and DWC202518 Monotherapy in Patients With Type 2 Diabetes Mellitus

This study aims to evaluate the efficacy and safety of initial combination therapy with DWP16001 and DWC202518 compared to DWP16001 monotherapy and DWC202518 monotherapy in patients with Type 2 Diabetes Mellitus

Inclusion Criteria:

1. Able and willing to cooperate and participate in this clinical study after understanding the study explanation, and capable of voluntarily signing the written informed consent form before any assessments are performed.

2. Male or female adult aged ≥18 and ≤80 years. Note: The minimum legal age of adult dependent on local regulations. The legal age of adult in Korea is 19 years, while in Indonesia, it is 18 years.

3. Have been diagnosed with T2DM based on American Diabetes Association (ADA) guidelines (2025) before screening.

4. Participants must meet one of the following conditions at Visit 1 (Screening):

   • Have an HbA1c ≥7.5% and ≤11% at Visit 1 (Screening) and either have never taken oral anti-diabetic medication since diagnosis or have not taken any oral anti-diabetic medication within 12 weeks prior to screening.
   • Have an HbA1c ≥6.5% and ≤10.5% at Visit 1 (Screening) and are currently taking one type of oral anti-diabetic medication at screening.

   Note: The HbA1c level at Visit 1 can be measured by the local laboratory.

5. Have an FPG <15 mmol/L (270 mg/dL), as measured by local laboratory at Visit 1.

6. Participants must meet all the following conditions at Visit 2 (Baseline):

   • Have an HbA1c ≥7.5% and ≤11%, as measured by the central laboratory at Visit 1-1.
   • Have an FPG <15 mmol/L (270 mg/dL), as measured by central laboratory at Visit 1-1.

7. Have a BMI ≥20 kg/m2 and ≤45 kg/m2 at screening.

8. Women of childbearing potential (WOCBP) must have a negative pregnancy test at screening. WOCBP and their partners must use highly effective, medically accepted contraception to prevent pregnancy and must not have pregnancy or fertility plans throughout the study and for at least 4 weeks after the last dose of study medication

9. Male participants must agree to use highly effective, medically accepted contraception and refrain from donating sperm throughout the study and for at least 4 weeks after the last dose of study medication

Exclusion Criteria:

• Type 1 diabetes mellitus, congenital diabetes, secondary diabetes, or history of diabetic ketoacidosis, diabetic coma, or precoma
• Severe diabetes-related complications, including proliferative diabetic retinopathy, advanced nephropathy, or severe diabetic neuropathy
• Clinically significant renal disease, severe gastrointestinal disease or surgery affecting gastrointestinal absorption, pancreatitis, clinically significant urinary/genital infections, dehydration requiring treatment, or uncontrolled thyroid disease
• Clinically significant cardiovascular or cerebrovascular disease within 6 months prior to screening, including myocardial infarction, unstable angina, stroke, clinically significant arrhythmia requiring treatment, or New York Heart Association (NYHA) class III-IV heart failure
• Active or untreated malignancy, or clinically significant malignancy within the previous 5 years (except adequately treated localized skin cancers or in situ carcinomas)
• Hematologic conditions that may interfere with HbA1c measurement
• Clinically significant endocrine disorders affecting glucose metabolism
• Known or suspected hypersensitivity to study treatment or related products
• Screening laboratory abnormalities including:

ㆍ Fasting C-peptide ≤0.60 ng/mL ㆍ Triglycerides >500 mg/dL ㆍ eGFR <60 mL/min/1.73m² ㆍ AST or ALT ≥3× upper limit of normal (ULN), or total bilirubin ≥2× ULN

• Positive hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection meeting protocol-defined criteria
• Uncontrolled hypertension (systolic blood pressure >180 mmHg and/or diastolic blood pressure >110 mmHg)
• Prior use of prohibited antidiabetic therapies, including prior antidiabetic combination therapy, thiazolidinediones within 12 weeks, or GLP-1 receptor agonists or insulin within 6 months before screening
• Use of weight-loss medications within 3 months prior to screening or between screening and baseline
• Use of systemic corticosteroids at pharmacologic doses within 1 month prior to screening or between screening and baseline