[Analysis of the efficacy of orlistat combined with pioglitazone and metformin in the treatment of obese patients with type 2 diabetes mellitus].

Objective: To evaluate the efficacy of orlistat combined with pioglitazone and metformin in the treatment of obese patients with type 2 diabetes mellitus (T2DM). Methods: A prospective multicenter randomized controlled trial. A total of 122 obese patients with T2DM were enrolled from November 2020 to April 2023 at Shanghai Tenth People's Hospital, Tong Ren Hospital Shanghai Jiao Tong University School of Medicine, Minhang Hospital of Fudan University, and Shanghai Traditional Chinese Medicine Hospital. Patients were randomly assigned (1∶1) via a central randomization system to either the control group or the orlistat group. Both groups received a combination preparation of pioglitazone and metformin. On this basis, the control group and the orlistat group took 120 mg of placebo or orlistat, respectively, three times a day. Changes in glycated hemoglobin (HbA1c), body composition, glucose metabolism and lipid metabolism were compared between the two groups after 12 weeks of treatment. Results: Among the 122 patients (68 males, 54 females), the age was (44.6±11.1) years, and the mean body mass index (BMI) was [M(Q₁,Q₃)] 31.2(29.4, 34.4) kg/m², with 62 patients in the control group and 60 patients in the orlistat group. At baseline, there were no statistically significant differences between the two groups in terms of age, gender, BMI, body composition, and indicators of glucose and lipid metabolism (all P0.05). After treatment, the orlistat group showed a greater reduction in fasting blood glucose compared to the control group [(-0.7±1.1) vs (-0.2±1.9) mmol/L, P=0.049]. Both groups exhibited lower HbA1c levels post-treatment(both P0.05), with no significant difference between the control and orlistat groups in post-treatment HbA1c (6.6%±1.2% vs 6.3%±0.6%) or HbA1c reduction (-0.6%±1.2% vs -0.7%±0.7%, all P0.05). The orlistat group demonstrated a significant decrease in the homeostasis model assessment of insulin resistance (HOMA-IR) compared to baseline [3.1(2.1, 5.2) vs 4.1(2.4,7.7), P0.001] and the control group post-treatment [3.1(2.1, 5.2) vs 4.1 (2.4,7.0), P=0.044]. Body weight and BMI were reduced in the orlistat group (both P0.05), whereas no significant changes were observed in the control group (both P0.05). The orlistat group also showed a greater reduction in abdominal subcutaneous fat area and visceral fat area compared to the control group (both P0.05). There were no statistically significant differences in total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and free fatty acids between the two groups before and after treatment (all P0.05). Conclusion: The combination of orlistat with pioglitazone and metformin effectively promotes weight loss, improves fat distribution, alleviates insulin resistance, and reduces fasting blood glucose in obese patients with T2DM.