聚乙二醇洛塞那肽对2型糖尿病合并代谢相关脂肪性肝病患者的疗效和安全性分析

Efficacy and Safety Analysis of Polyethylene Glycol Loxenatide in Patients with Type 2 Diabetes Mellitus and Metabolic Dysfunction-Associated Steatotic Liver Disease

摘要: 目的：评估聚乙二醇洛塞那肽对2型糖尿病合并代谢相关脂肪性肝病患者的临床疗效。方法：回顾性纳入2022年3月至2025年3月青岛市公共卫生临床中心内科诊疗中心确诊的2型糖尿病合并代谢相关脂肪性肝病患者，根据治疗方式的不同分为二甲双胍组和洛塞那肽组。二甲双胍组患者应用盐酸二甲双胍缓释片治疗，洛塞那肽组患者应用盐酸二甲双胍缓释片联合聚乙二醇洛塞那肽注射液治疗。连续治疗12周后，收集并分析比较2组患者治疗前后的糖代谢及脂代谢指标，评估聚乙二醇洛塞那肽对2型糖尿病合并非酒精性脂肪性肝病患者的疗效。结果：本研究共纳入85例患者，其中二甲双胍组43人(男性23名，女性20名)，洛塞那肽组42人(男性28名，女性14名)。二甲双胍组年龄59.12 ± 9.53岁，洛塞那肽组年龄56.29 ± 10.00岁。经治疗后二甲双胍组空腹血糖、糖化血红蛋白分别从8.75 ± 2.55 mmol/L、7.45% ± 1.52%降低为7.80 ± 2.09 mmol/L、6.93% ± 1.09% (P均 > 0.05)，洛塞那肽组空腹血糖、糖化血红蛋白分别从9.11 ± 2.56 mmol/L、7.82% ± 1.34%降低为6.74 ± 1.63 mmol/L、6.45% ± 0.89% (均P < 0.05)，在治疗后洛塞那肽组糖代谢指标均低于二甲双胍组，差异有统计学意义(P < 0.05)。二甲双胍组甘油三酯、总胆固醇、低密度脂蛋白胆固醇、载脂蛋白A1、载脂蛋白B分别从2.22 ± 1.23 mmol/L、5.27 ± 1.17 mmol/L、3.27 ± 1.09 mmol/L、1.37 ± 0.21 mmol/L、1.11 ± 0.31 mmol/L变为2.08 ± 1.52 mmol/L、5.08 ± 1.07 mmol/L、3.11 ± 0.89 mmol/L、1.29 ± 0.17 mmol/L、0.99 ± 0.22 mmol/L，其中ApoB下降明显(P < 0.05)。而洛塞那肽组患者的甘油三酯、总胆固醇、低密度脂蛋白胆固醇、载脂蛋白A1、载脂蛋白B分别从2.66 ± 2.24 mmol/L、5.41 ± 1.19 mmol/L、3.24 ± 0.96 mmol/L、1.29 ± 0.27 mmol/L、1.05 ± 0.28 mmol/L降为1.72 ± 1.15 mmol/L、4.69 ± 1.02 mmol/L、2.86 ± 0.85 mmol/L、1.15 ± 0.23 mmol/L、0.93 ± 0.21 mmol/L，差异均有统计学意义(均P < 0.05)。经治疗12周后二甲双胍组ALT水平较治疗前下降(P < 0.05)，WBC、PLT、AST、ALB水平未观察到明显改变(P > 0.05)。洛塞那肽组在治疗12周后WBC、PLT、ALT、AST、ALB水平较治疗前未观察到明显改变(P > 0.05)。两组在观察期间均未发生明显不良反应。结论：聚乙二醇洛塞那肽对于2型糖尿病合并代谢相关脂肪性肝病患者的糖代谢及脂代谢指标具有良好的临床疗效，且安全性良好。

Abstract: Objective: To evaluate the clinical efficacy of PEX-168 in patients with type 2 diabetes mellitus complicated with metabolic dysfunction-associated steatotic liver disease (MASLD). Method: Patients diagnosed with type 2 diabetes mellitus complicated with MASLD at the Internal Medicine Diagnosis and Treatment Center of Qingdao Public Health Clinical Center from March 2022 to March 2025 were retrospectively included. They were divided into the metformin group and the loxenatide group according to different treatment methods. Patients in the metformin group were treated with metformin hydrochloride sustained-release tablets, while those in the loxenatide group were treated with metformin hydrochloride sustained-release tablets combined with PEX-168 injection. After 12 consecutive weeks of treatment, the glucose metabolism and lipid metabolism indicators of the two groups of patients before and after treatment were collected and analyzed and compared to evaluate the efficacy of PEX-168 in patients with type 2 diabetes mellitus complicated with MASLD. Result: A total of 85 patients were included in this study, among whom 43 were in the metformin group (23 males and 20 females) and 42 were in the loxenatide group (28 males and 14 females). The age of the metformin group was 59.12 ± 9.53 years old, and that of the loxenatide group was 56.29 ± 10.00 years old. After treatment, the fasting blood glucose and glycated hemoglobin in the metformin group decreased from 8.75 ± 2.55 mmol/L and 7.45% ± 1.52% to 7.80 ± 2.09 mmol/L and 6.93% ± 1.09% respectively (all P > 0.05). The fasting blood glucose and glycated hemoglobin in the loxenatide group decreased from 9.11 ± 2.56 mmol/L and 7.82% ± 1.34% to 6.74 ± 1.63 mmol/L and 6.45% ± 0.89% respectively (all P < 0.05). After treatment, the glucose metabolism indicators in the loxenatide group were lower than those in the metformin group. The difference was statistically significant (P < 0.05). The levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 and apolipoprotein B in the metformin group were 2.22 ± 1.23 mmol/L, 5.27 ± 1.17 mmol/L and 3.27 ± 1.09, respectively mmol/L, 1.37 ± 0.21 mmol/L, and 1.11 ± 0.31 mmol/L changed to 2.08 ± 1.52 mmol/L, 5.08 ± 1.07 mmol/L, 3.11 ± 0.89 mmol/L, and 1.29 ± 0.17 mmol/L, 0.99 ± 0.22 mmol/L, among which ApoB decreased significantly (P < 0.05). The levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 and apolipoprotein B in the loxenatide group were 2.66 ± 2.24 mmol/L, 5.41 ± 1.19 mmol/L, 3.24 ± 0.96 mmol/L and 1.29 ± 0.27, respectively mmol/L and 1.05 ± 0.28 mmol/L decreased to 1.72 ± 1.15 mmol/L, 4.69 ± 1.02 mmol/L, 2.86 ± 0.85 mmol/L, 1.15 ± 0.23 mmol/L, and 0.93 ± 0.21 mmol/L. The differences were all statistically significant (all P < 0.05). After 12 weeks of treatment, the ALT level in the metformin group decreased compared with that before treatment (P < 0.05), while no significant changes were observed in the levels of WBC, PLT, AST and ALB (P > 0.05). After 12 weeks of treatment, no significant changes were observed in the levels of WBC, PLT, ALT, AST and ALB in the loxenatide group compared with those before treatment (P > 0.05). No obvious adverse reactions occurred in either group during the observation period. Conclusion: PEX-168 has a good clinical efficacy in the glucose metabolism and lipid metabolism indicators of patients with type 2 diabetes mellitus complicated with MASLD, and has good safety.