胰升糖素样肽1受体激动剂联合二甲双胍对超重/肥胖多囊卵巢综合征患者糖脂代谢及生殖功能的影响

Effects of glucagon-like peptide-1 receptor agonis combined with metformin on glucolipid metabolism and reproductive function in overweight/obese polycystic ovarian syndrome patients

目的观察胰升糖素样肽1受体激动剂(glucagon-like peptide-1 receptor agonist, GLP-1RA)联合二甲双胍对超重/肥胖多囊卵巢综合征(polycystic ovarian syndrome, PCOS)患者糖脂代谢及生殖功能的影响。方法选取2017年7月至2022年7月于陆军军医大学第二附属医院内分泌科接受12周(利拉鲁肽+二甲双胍或艾塞那肽+二甲双胍)治疗的200例超重/肥胖PCOS患者。回顾性分析治疗前后人体测量、糖脂代谢、月经周期、性激素、卵巢多囊样改变等临床指标的变化。结果在改善代谢方面, 治疗后受试者体重、体重指数、腰围、臀围、腰臀比、谷草转氨酶、γ-谷氨酰转移酶、HbA1C、空腹血糖、胰岛素(包括空腹、30、60、120及180 min)、稳态模型评估的胰岛素抵抗指数、胰岛素曲线下面积、三酰甘油、总胆固醇较治疗前明显下降, 差异有统计学意义(P<0.05或P<0.01或P<0.001)。在生殖功能方面, 治疗后受试者睾酮、促黄体生成素、促卵泡激素/促黄体生成素、游离雄激素指数较前下降(P<0.001), 性激素结合球蛋白较前升高(P<0.01)。孕酮、催乳素、促卵泡刺激素、硫酸脱氢表雄酮较治疗前差异无统计学意义(P>0.05);建立规律月经周期的受试者占比由23.53%上升至57.52%, 卵巢多囊样改变的受试者占比从65.30%下降至50.32%, 且出现优势卵泡的占比从0上升至18.30%, 差异有统计学意义(P<0.05或P<0.01)。部分患者(25.49%)用药后出现恶心、腹泻、腹胀、呕吐等不良反应。结论 GLP-1RA联合二甲双胍可同时有效改善超重/肥胖PCOS患者糖脂代谢紊乱及生殖功能障碍。

Objective To observe the effects of glucagon-like peptide-1 receptor agonist(GLP-1RA)combined with metformin on glucolipid metabolism and reproductive function in overweight/obesity polycystic ovarian syndrome(PCOS)patients.Methods Retrospectively analyzed changes in clinical parameters of body measurements,glucolipid metabolism,menstrual cycle,hormones,and polycystic ovary in 200 overweight/obese PCOS Patients who received 12 weeks of treatment(liraglutide+metformin or exenatide+metformin)in the Department of Endocrinology at the Second Affiliated Hospital of Army Medical University from July 2017 to July 2022.Results In terms of metabolism improvement,body weight,body mass index,waist circumference,hip circumference,waist-hip ratio,glutamic-oxalacetic transaminase,γ-glutamyltransferase,glycosylated hemoglobin,fasting blood glucose,insulin(including fasting,30,60,120,and 180 minutes),homeostasis model assessment for insulin resistance,area under curve-insulin,triglyceride,and total cholesterol were significantly decreased after treatment(P<0.05 or P<0.01 or P<0.001).In terms of reproductive function,testosterone,luteinizing hormone,follicle stimulating hormone/luteinizing hormone and free androgen index were decreased(P<0.001),while sex hormone-binding globulin was increased(P<0.01).There were no significant differences in progesterone,prolactin,follicle-stimulating hormone and dehydroepiandrosterone sulfate compared with before treatment(P>0.05).The proportion of subjects with regular menstrual cycle increased from 23.53%to 57.52%(P<0.05).The proportion of subjects with polycystic ovarian changes decreased from 65.30%to 50.32%,and the proportion with dominant follicles increased from zero to 18.30%(P<0.05 or P<0.01).Some patients(25.49%)experienced adverse reactions such as nausea,diarrhea,abdominal distension,and vomiting after medication.Conclusion The combination of GLP-1RA and metformin effectively improves glucose lipid metabolism disorder and reproductive dysfunction in overweight/obese PCOS patients.