A Phase 2 Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of SAL0150 Tablets in Subjects With Type 2 Diabetes Mellitus

Inclusion Criteria:

• Male or female, age above or equal to 18 years at the time of signing informed consent;

• Diagnosed with type 2 diabetes mellitus according to the World Health Organization (WHO) diagnostic criteria for diabetes (2011) and classification criteria, and with a disease duration of at least 3 months at screening;

• Participants who had received any of the following glycemic control regimens prior to screening and had inadequate glycemic control:

  • Diet and exercise intervention alone for at least 8 weeks;
  • Diet and exercise intervention combined with monotherapy with a stable dose of metformin (daily dose ≥ 1000 mg) for at least 6 weeks;

• HbA1c ≥7.5% and ≤11.0% at screening as assessed by the local laboratory;

• Body mass index (BMI) ≥20.0 kg/m2 and ≤42.0 kg/m2 at screening/randomization;

• No significant change in body weight within 3 months prior to screening (weight gain or loss < 5%);

• Able to understand the procedures and methods of this study, willing to strictly follow the clinical trial protocol to complete this trial, and voluntarily sign the informed consent form.

Exclusion Criteria:

• Any of the following endocrine-related medical histories or evidence prior to screening:

  1. Diagnosis or suspected type 1 diabetes, special types of diabetes (except gestational diabetes) or secondary diabetes;
  2. History of acute diabetic complications within 6 months prior to screening, such as diabetic ketoacidosis, hyperglycemic hyperosmolar state, or lactic acidosis;
  3. Having severe chronic complications of diabetes at screening, including but not limited to: proliferative diabetic retinopathy, severe diabetic macular edema, or severe non-proliferative diabetic retinopathy requiring treatment during the study period; intermittent claudication, diabetic foot ulcers; gastroparesis, painful neuropathy, a resting tachycardia, orthostatic hypotension;
  4. History of level 3 hypoglycemia within 6 months prior to screening (manifesting as central nervous system symptoms or abnormal changes in mental behavior);
  5. Has a personal history or first degree relative family history of multiple endocrine neoplasia syndrome type 2 (MEN2) or medullary thyroid carcinoma (MTC);
  6. Abnormal thyroid function that is not stably controlled with medication at screening (for at least 3 months);
  7. Having other serious endocrine system diseases that affect glucose metabolism, such as multiple endocrine neoplasia, Cushing's syndrome, etc.;

• Any of the following medical history or evidence prior to screening:

  1. History of the following serious cardiovascular or cerebrovascular diseases within 6 months prior to screening: such as decompensated heart failure (New York Heart Association [NYHA] functional class III or IV), acute myocardial infarction, unstable angina attacks, or cardiac surgery such as coronary stent implantation or coronary artery bypass grafting (diagnostic angiography is permitted); new-onset stroke, transient ischemic attack, or recurrent syncope;
  2. Uncontrolled hypertension during screening: seated systolic blood pressure (SBP) ≥160 mmHg and/or seated diastolic blood pressure (DBP) ≥100 mmHg; or hypotension (SBP <90 mmHg);
  3. Have obvious hematologic diseases or any diseases that cause hemolysis or erythrocyte instability, including but not limited to: hemolytic anemia, aplastic anemia, myelodysplastic syndrome, thalassemia, etc.;
  4. Have a history of acute or chronic pancreatitis, symptomatic gallbladder or biliary tract disease (such as common bile duct stones, cholelithiasis with multiple stones, etc.; if the common bile duct stones have been cleared or the subject has previously undergone cholecystectomy, may be enrolled after assessment by the investigator), or a history of pancreatic injury and other high-risk factors that may lead to pancreatitis;
  5. Have a history of severe gastrointestinal diseases (such as active ulcer, inflammatory bowel disease) occurring within 6 months prior to screening, or have undergone gastrointestinal surgery (except appendectomy, polypectomy or other gastrointestinal endoscopic surgeries that are judged by the investigator to have no significant effect on gastrointestinal motility), or have clinically significant gastric emptying abnormalities(such as pyloric obstruction, intestinal obstruction, etc.), or have been taking drugs that directly affect gastrointestinal motility for a long time(such as domperidone, mosapride, cisapride, etc.);
  6. Severe trauma or acute infection within 4 weeks prior to screening that could potentially affect glycemic control;
  7. Any of the following clinically significant arrhythmias occurring at screening or randomization: second or third degree atrioventricular block, long QT syndrome, or other severe arrhythmias that the investigator deems unsuitable for inclusion in this study;
  8. History of malignant tumor within 5 years prior to screening (except clinically cured local skin basal cell carcinoma or carcinoma in situ); Comorbid psychiatric illness or language barriers, unwilling or unable to adequately understand and cooperate.

• Use of any of the following medications or treatments prior to screening:

  1. Use of glucose-lowering medications other than metformin within 2 months prior to screening (except for cumulative duration ≤7 days);
  2. Use of GLP-1RA analogs or related compounds within 3 months prior to screening; known or suspected allergy to the investigational drug or related products; discontinued medication more than 3 months prior to screening due to intolerance or lack of efficacy must also be excluded;
  3. Use of weight-loss medications within 3 months prior to screening, or undergoing surgery that could lead to weight instability, or plan to undergo bariatric surgery or weight-loss procedures/surgical treatments during the trial; Currently receiving or having received chronic (>2 weeks) systemic glucocorticoid treatment within 3 months prior to screening (excluding topical, intraocular, intranasal, single intra-articular injection, or inhaled formulations), or having received such treatment within 4 weeks prior to screening.

• Any of the following laboratory abnormalities at screening:

  1. Aspartate aminotransferase (AST) ≥3× upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3× ULN;
  2. Total bilirubin (TBIL) >1.5× ULN;
  3. Amylase and/or lipase ≥ 2×ULN;
  4. Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m² (estimated using the CKD-EPI formula) or urinary albumin to creatinine ratio(UACR) ≥ 300 mg/g;
  5. Triglycerides (TG) > 5.65 mmol/L;
  6. Calcitonin ≥ 50 ng/L;
  7. Thyroid-stimulating hormone (TSH) > 6.0 mIU/L or < 0.4 mIU/L; Positive result on hepatitis B surface antigen (HBsAg) and HBV-DNA quantitative test results above the upper limit of the local laboratory reference range, or positive hepatitis C virus antibody (HCV-Ab) and HCV-RNA test results above the upper limit of the local laboratory reference range, or positive human immunodeficiency virus(HIV) antibody, or positive treponema pallidum antibody.

• History of substance abuse or alcohol abuse within 6 months prior to screening (consuming 14 units of alcohol per week: 1 unit = 285 mL of beer, 25 mL of spirits, or 100 mL of wine);

• Participation in a clinical trial of another drug or medical device within 3 months prior to screening, and receipt of investigational medication or medical device intervention;

  • Undergoing major surgical treatment within 3 months prior to screening, or having elective surgery scheduled during the study period (excluding minor surgeries under local anesthesia);

• Have donated blood or lost ≥400 mL of blood, received blood transfusion or used blood products within 3 months prior to screening; Pregnancy, lactation, or have tested positive for pregnancy; participants or their partners who are unwilling to use effective contraception from the time of signing the informed consent form until 3 months after the last dose.

• Any other factor that, in the investigator's opinion, may affect the efficacy or safety assessment of this study or make the subject unsuitable for participation in this clinical trial (including, but not limited to, poor compliance as judged by the investigator, or living too far away to attend scheduled follow-up visits).