Enhancing Glycemic Control through Orlistat Combination Therapy with Pioglitazone and Metformin in Patients with Obesity Type 2 Diabetes—A Multicenter Randomized Controlled Trial

Introduction and Objective: Obesity further impairs blood glucose regulation, so patients with obesity and type 2 diabetes should undergo aggressive weight loss treatment. We aimed to evaluate the efficacy of orlistat in patients with obesity and type 2 diabetes treated with pioglitazone-metformin. Methods: In this double-blind, placebo-controlled, 12-week, multicenter trial, patients aged 18-65 years with type 2 diabetes and a BMI > 28 kg/m² on pioglitazone-metformin. They were randomly assigned to receive placebo or 120 mg orlistat three times daily. The primary endpoint was HbA1c change from baseline to week 12. Secondary endpoints included improvements in blood glucose, HOMA-IR, body weight, and abdominal obesity. Results: After 12 weeks, HbA1c improvement in the orlistat group was not significant. However, insulin resistance improved notably, with HOMA-IR decreasing by -15.6% vs -7.86% in the placebo group (P<0.05). Blood glucose levels also improved significantly; fasting blood glucose dropped by -0.73 vs -0.17 mmol/L (P<0.05). This improvement is linked to orlistat’s weight loss effect. At week 12, the orlistat group had significantly lower BMI (30.16 vs 32.70 kg/m², P<0.001) and reduced subcutaneous fat (246.43 vs 307.38 cm²) and visceral fat (120.70 vs 142.46 cm², P<0.05) compared to the placebo group. Conclusion: Orlistat is effective for patients with obesity and type 2 diabetes who are receiving pioglitazone-metformin therapy, it reduces body weight, improves fat distribution, alleviates insulin resistance, and enhances glycemic control. Disclosure: J. Liu: None. H. You: None. X. Wen: None. Y. Fang: None. L. Bu: None. S. Qu: None.