The Effectiveness of Liraglutide Combined with Metformin in Improving Glycolipid Metabolism and Hormonal Levels in Polycystic Ovary Syndrome: A Meta-Analysis
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摘要:
目的 系统性评价利拉鲁肽联合二甲双胍对多囊卵巢综合征（PCOS）患者糖脂代谢、性激素、生殖功能及胃肠道反应的影响。 方法 检索PubMed、万方医学网、万方数据库、CNKI中国知网、维普期刊等数据库，收集2011年1月至2022年8月公开发表的利拉鲁肽联合二甲双胍治疗多囊卵巢综合征的随机对照研究，使用Revman5.4进行荟萃分析。 结果 共纳入16项病例对照研究，包括了 1436 例患者，与单用二甲双胍相比较，利拉鲁肽联合二甲双胍可显著降低PCOS患者的空腹血糖、餐后2 h血糖、HbA1C、HOMA-IR、FINS、BMI及LH、FSH、总睾酮（P < 0.05），改善了PCOS患者的血脂水平、促使其月经周期的建立，提高了PCOS患者的正常排卵率、自然受孕率，但利拉鲁肽联合二甲双胍组患者的胃肠道反应发生率明显增加，差异具有统计学意义（P < 0.05）。结论 利拉鲁肽联合二甲双胍可改善多囊卵巢综合征（PCOS）患者的糖脂代谢，降低LH、FSH、总睾酮水平，促使月经周期的建立，提高排卵率及受孕率，但胃肠道反应明显增加。 Abstract:Objective To systematically evaluate the effects of liraglutide combined with metformin on glucose and lipid metabolism, sex hormones, reproductive function, and gastrointestinal reactions in patients with polycystic ovary syndrome （PCOS）. Methods We searched databases such as PubMed, WanFang Medical Network, WanFang Database, China National Knowledge Infrastructure（CNKI）, and VIP Journals to collect randomized controlled trials published from January 2011 to August 2022 on the treatment of polycystic ovary syndrome with liraglutide combined with metformin, using Revman 5.4 for the meta-analysis. Results A total of 16 case-control studies were included, involving 1, 436 patients. Compared to metformin alone, the combination of liraglutide and metformin significantly lowered fasting blood sugar, postprandial blood glucoseafter 2 hours, HbA1c, HOMA-IR, FINS, BMI, as well as LH, FSH, and total testosterone in patients with PCOS. It improved lipid levels, helped establish menstrual cycles, and increased the normal ovulation rate and natural conception rate in these patients. However, there was a significantly higher incidence of gastrointestinal reactions in the liraglutide plus metformin group, and the difference was statistically significant （P < 0.05）. Conclusion: The combination of liraglutide and metformin can improve glucose and lipid metabolism in patients with polycystic ovary syndrome （PCOS）, reduce levels of LH, FSH, and total testosterone, help establish regular menstrual cycles, and increase ovulation and pregnancy rates, but it significantly increases gastrointestinal side effects. -
Key words:
- Liraglutide /
- Metformin /
- Polycystic ovary syndrome /
- Glycolipid metabolism
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图 1 联合治疗组与对照组空腹血糖的森林图
Figure 1. Forest plot of fasting blood glucose between the combination therapy group and the control group
图 2 联合治疗组与对照组餐后2 h血糖的森林图
Figure 2. Forest plot of 2-hour postprandial blood glucose levels between the combination therapy group and the control group
图 3 联合治疗组与对照组糖化血红蛋白的森林图
Figure 3. Forest plot of glycated hemoglobin between the combination therapy group and the control group
图 4 联合治疗组与对照组胰岛素抵抗指数的森林图
Figure 4. Forest plot of insulin resistance index between the combination therapy group and the control group
图 5 联合治疗组与对照组空腹胰岛素（FINS）的森林图
Figure 5. Forest plot of fasting insulin （FINS） between the combination therapy group and the control group
图 6 联合治疗组与对照组体重指数（BMI）的森林图
Figure 6. Forest plot of body mass index （BMI） between the combination therapy group and the control group
图 7 联合治疗组与对照组促黄体生成素的森林图
Figure 7. Forest plot of luteinizing hormone levels between the combination therapy group and the control group
图 8 联合治疗组与对照组促卵泡刺激素的森林图
Figure 8. Forest plot of follicle stimulating hormone between the combination therapy group and the control group
图 9 联合治疗组与对照组总睾酮的森林图
Figure 9. Forest plot of total testosterone between the combination therapy group and the control group
图 10 联合治疗组与对照组总胆固醇（TC）的森林图
Figure 10. Forest plot of total cholesterol （TC） between the combination therapy group and the control group
图 11 联合治疗组与对照组甘油三酯（TG）的森林图
Figure 11. Forest plot of triglycerides （TG） between the combination therapy group and the control group
图 12 联合治疗组与对照组低密度脂蛋白（LDL-C）的森林图
Figure 12. Forest plot of low-density lipoprotein （LDL-C） in the combination therapy group and the control group
图 13 联合治疗组与对照组高密度脂蛋白（HDL-C）的森林图
Figure 13. Forest plot of high-density lipoprotein （HDL-C） between the combination therapy group and the control group
图 14 联合治疗组与对照组患者月经周期建立的森林图
Figure 14. Forest plot of menstrual cycle establishment between the combination therapy group and the control group patients
图 15 联合治疗组与对照组患者正常排卵率的森林图
Figure 15. Forest plot of normal ovulation rate between the combination therapy group and the control group patients
图 16 联合治疗组与对照组患者自然受孕率的森林图
Figure 16. Forest plot of natural conception rates between the combination therapy group and the control group patients
图 17 联合治疗组与对照组患者胃肠道反应的森林图
Figure 17. Forest plot of gastrointestinal reactions between patients in the combination therapy group and the control group
表 1 纳入荟萃分析的16篇文献资料
Table 1. 16 studies included in the meta-analysis
第一作者/发表年份 研究起始时间 联合治疗组（n） 对照组（n） 分组方法 治疗时间（周） 疗效指标 黄昭穗，2015[4] 2011.3 -2014.3 87 85 随机数字表法 24 ①②③④⑤⑥⑦⑧⑨⑩⑪⑫⑬⑭⑮⑯⑰ 郝建民，2020[5] 2017.6 -2018.12 93 93 随机数字表法 12 ①②④⑤⑥⑨⑰ 郑亮，2022[6] 2018.5 -2020.12 75 75 随机抽签法 24 ①②③④⑤⑥⑦⑧⑨⑩⑪⑫⑬⑭⑮⑯⑰ 赵丹，2019[7] 2015.1 -2018.10 30 30 患者选择不同治疗方案 24 ①②③④⑥⑦⑧⑨⑰ 谭明灯，2022[8] 2018.11 -2020.11 46 46 随机数字表法 16 ①②③④⑦⑧⑨⑩⑪⑫⑬⑭⑮⑯⑰ 王爱媛，2020[9] 2018.1 -2020.2 30 30 奇偶数法 4 ①②③④⑥ 杨莉，2022[10] 2018.5 -2020 .550 50 随机数字表法 24 ①②④⑥⑦⑧⑨ 杨茜，2021[11] 2017.3 -2020.3 50 50 奇偶数法 12 ①②④⑤⑥⑦⑧⑨⑭⑮⑯⑰ 张波，2019[12] 2017.1 -2019.1 42 42 随机数字表法 16 ①②③⑩⑪⑫⑬⑰ 宛光彩，2021[13] 2018.1 -2019.1 30 30 随机数字表法 24 ①②③④⑦⑧⑰ 孙海云，2021[14] 2019.3 -2020.3 56 56 随机分组 16 ①④⑤⑥⑦⑧⑨⑰ 孙晖，2020[15] 2018.1 -2020.1 37 37 随机数字表法 24 ①②③④⑦⑧⑨⑭⑮⑰ 仉媛媛，2020[16] 2018.1 -2019.6 41 41 随机分组 12 ①②④⑤⑨ Vesna Salamun，2018[17] 2014.9 -2015.5 13 14 随机分组 12 ①②④⑤⑥⑨⑰ Mojca Jensterle
Sever，2014[18]2011.11 -2012.5 11 14 随机分组 12 ①②④⑤⑥⑨⑪⑫⑬⑰ Chuan Xing，2022[19] 2021.1 -2022.1 27 25 随机分组 12 ①④⑤⑥⑦⑧⑨ 联合治疗组：利拉鲁肽+二甲双胍；对照组：二甲双胍，疗效指标：①空腹血糖，②餐后2 h血糖，③糖化血红蛋白，④胰岛素抵抗指数，⑤空腹胰岛素，⑥BMI，⑦促黄体生成素，⑧促卵泡刺激素，⑨总睾酮，⑩总胆固醇，⑪甘油三酯，⑫低密度脂蛋白，⑬高密度脂蛋白，⑭建立月经周期，⑮正常排卵率，⑯自然受孕率，⑰胃肠道反应。 
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