Efficacy and Safety of Henagliflozin, Retagliptin, and Metformin Extended-Release Tablets in Chinese Patients With Type 2 Diabetes Mellitus

Prior treatment

• Known or suspected hypersensitivity to the investigational product or related compounds.
• Participation in any other investigational drug trial within 3 months prior to the start of this study.
• Use of traditional Chinese herbal medicine for glycemic control within 2 months prior to screening (except for cumulative use ≤7 days).
• Severe infection, significant trauma, or major surgery within 30 days prior to screening.

Other illness

• Type 1 diabetes mellitus, monogenic diabetes, diabetes due to pancreatic injury, or other forms of secondary diabetes (e.g., diabetes secondary to Cushing's syndrome or acromegaly).
• History of acute metabolic complications (e.g., ketoacidosis, lactic acidosis, hyperosmolar coma/state) within the past 6 months.
• History of decompensated heart failure (NYHA Class IV), unstable angina, stroke or transient ischemic attack, myocardial infarction, severe arrhythmia, or cardiac surgery or vascular reconstruction (including coronary artery bypass grafting or percutaneous coronary intervention) within the past 6 months.
• History of acute or chronic pancreatitis.
• Patients with malignancy and a life expectancy of less than one year, active tuberculosis, or acute infection.
• Current or history of recurrent urinary tract infections and/or genital infections.
• Patients with a history of hypertension whose blood pressure remains uncontrolled despite antihypertensive medication: systolic blood pressure (SBP) \>180 mmHg and/or diastolic blood pressure (DBP) \>110 mmHg.
• Any other condition that, in the investigator's judgment, renders the patient unsuitable for participation in this clinical trial.

Lab values

• Fasting C-peptide \<1.0 ng/mL (0.34 nmol/L) as measured by the local laboratory.
• Moderate to severe renal impairment (eGFR \<45 mL/min/1.73m²), end-stage renal disease, or patients on dialysis.
• Alanine aminotransferase (ALT) \>3.0 x ULN and/or aspartate aminotransferase (AST) \>3.0 x ULN and/or total bilirubin \>2.0 x ULN (upper limit of normal).

Other

• Systolic blood pressure \<90 mmHg at the screening visit, or patients judged by the clinician to be hypovolemic.
• Men or women of childbearing potential unwilling to use effective contraception during the trial, or women who are pregnant or breastfeeding.

• Male or female aged 18 to 70 years (inclusive) at the time of signing the informed consent form.
• Diagnosed with type 2 diabetes mellitus.
• Voluntarily participate in this study and sign the informed consent form. If a subject is unable to read the informed consent form (e.g., an illiterate subject), an impartial witness must be present during the entire informed consent discussion and must also sign the consent form.
• At screening, the subject must meet either of the following two criteria:
  • Newly diagnosed with type 2 diabetes within 90 days prior to screening, with no prior use of any antidiabetic medication, and a screening HbA1c level between 8.0% and 11.0% (inclusive).
  • Treated with any one oral antidiabetic drug \[metformin (with a stable daily dose ≥1000 mg or the maximum tolerated dose documented in the patient's medical record), an alpha-glucosidase inhibitor, a sulfonylurea, a glinide, a thiazolidinedione, a sodium-glucose cotransporter-2 inhibitor (SGLT2i), a dipeptidyl peptidase-4 inhibitor (DPP-4i), a glucokinase activator, or an oral glucagon-like peptide-1 receptor agonist\] for at least 60 days prior to screening, with a screening HbA1c level between 7.0% and 11.0% (inclusive). The subject should have been on a stable dose of the medication for at least 30 days prior to screening.
• Body Mass Index (BMI) \>19 kg/m² and ≤40.0 kg/m².