This study compares the efficacy and safety of sitagliptin phosphate combined with gliclazide sustained-release tablets versus metformin in treatment-naïve patients with type 2 diabetes mellitus (T2DM) and glucotoxicity. The trial assesses glycemic control, patient compliance, and adverse events over a 12-week period using a randomized controlled design to determine the non-inferiority of the combined treatment.

In this single-center, prospective, randomized controlled non-inferiority study, treatment-naïve patients with T2DM and glucotoxicity were enrolled to evaluate the comparative efficacy and safety of two therapeutic regimens. The study investigates the combination of sitagliptin phosphate with gliclazide sustained-release tablets against metformin alone. Participants were randomized and monitored for 12 weeks, with primary outcomes focusing on fasting plasma glucose (FPG) levels, body weight changes, and hypoglycemic events. The study also explores the impact of treatment on β-cell function and insulin sensitivity, utilizing pharmacogenomic analysis to evaluate genetic factors influencing treatment response.

Inclusion Criteria:

• Diagnosed with Type 2 Diabetes Mellitus (T2DM) and glucotoxicity.
• Body Mass Index (BMI) between 18 and 30 kg/m².
• Fasting plasma glucose (FPG) levels ≥ 200 mg/dL and glycated hemoglobin (HbA1c) ≥ 9.0%.
• Normal hepatic and renal functions (ALT and AST ≤ 2.5 times the upper limit of normal; serum creatinine within normal limits).
• Capable of adhering to the prescribed anti-diabetic regimen and dietary guidelines.

Exclusion Criteria:

• Diagnosis of Type 1 Diabetes Mellitus.
• Hepatic or renal dysfunction (serum creatinine > 1.2 times the upper limit of normal).
• Prior use of hypoglycemic medications before screening.
• History of severe ketosis, ketoacidosis, or hyperosmolar hyperglycemic state.
• Current treatment with corticosteroids, immunosuppressive agents, or cytotoxic drugs.
• Major systemic diseases (e.g., cardiovascular, respiratory, neurological).
• Pregnant or breastfeeding women.
• Known allergies to sitagliptin or gliclazide.
• Poor compliance potential as assessed by the investigator.