Regimen Transition After Short-Term Intensive Insulin Therapy in Type 2 Diabetes

Inclusion criteria

• Diagnosed with type 2 diabetes mellitus (T2DM) with a disease duration of >1 year and <15 years.
• On a stable dose of at least one oral antidiabetic drug (OAD) for ≥3 months.
• HbA1c at screening: >8.0% if on a single OAD; >7.5% if on more than one OAD (centralized laboratory testing, or results from medical centers participating in the National Glycohemoglobin Standardization Program).
• Age 18-70 years.
• Body mass index (BMI) 20-35 kg/m².
• Able and willing to comply with study requirements, including continuous glucose monitoring, self-monitoring of blood glucose, lifestyle management, and insulin-based glycemic management.
• Agreement to use effective contraception during the study.
• Willingness to provide written informed consent.

Exclusion criteria

• Diagnosis of type 1 diabetes mellitus or other specific types of diabetes.
• Receipt within 3 months prior to screening of premixed insulin therapy and/or basal-bolus insulin therapy and/or basal insulin plus OAD therapy for ≥7 cumulative days; or receipt within 1 year prior to screening of intensive insulin therapy (insulin pump or multiple daily injections); or receipt within 3 months prior to screening of GLP-1 receptor agonists; or inability to tolerate protocol-specified doses.
• Known hypersensitivity or intolerance to study medications.
• Acute diabetic complications (including diabetic ketoacidosis, hyperosmolar hyperglycemic state, or lactic acidosis).
• Severe microvascular complications: proliferative diabetic retinopathy; albumin excretion rate (AER) >300 mg/g or proteinuria >0.5 g/day; uncontrolled painful diabetic neuropathy or significant autonomic neuropathy. Severe macrovascular complications: hospitalization for acute cerebrovascular accident, acute coronary syndrome, peripheral artery disease requiring intervention or amputation within the previous 12 months; unstable angina, myocardial infarction, uncontrolled arrhythmia, or severe heart failure (New York Heart Association [NYHA] class ≥III).
• Persistent blood pressure >180/110 mmHg, or uncontrolled above 160/110 mmHg within 1 week.
• Estimated creatinine clearance <45 mL/min/1.73 m² (calculated by CKD-EPI formula); alanine aminotransferase ≥2.5 × upper limit of normal (ULN); or total bilirubin ≥1.5 × ULN.
• Hemoglobin <100 g/L or requiring regular blood transfusions.
• Use within 12 weeks prior to screening of medications affecting glycemic control for >1 cumulative week, including oral/intravenous glucocorticoids, growth hormone, estrogen/progestins, high-dose diuretics, or antipsychotics. Exceptions: low-dose diuretics used for antihypertensive purposes (HCTZ <25 mg/day, indapamide ≤1.5 mg/day) and physiological thyroid hormone replacement therapy.
• Uncontrolled endocrine disorders.
• History or family history of medullary thyroid carcinoma, or history of multiple endocrine neoplasia syndrome type 2 (MEN2).
• Psychiatric illness or communication disorders.
• Systemic infection, severe comorbid conditions, malignancy, or chronic diarrhea.
• Pregnancy, lactation, or women of childbearing potential unwilling to use contraception during the study.
• Uncooperative participants, inability to comply with follow-up, or judged by investigators as unlikely to complete the study.
• Any other condition deemed unsuitable by investigators, including history of acute pancreatitis, rapidly progressing gallstones, or chronic cholecystitis.