二甲双胍与司美格鲁肽联合治疗对超重/肥胖多囊卵巢综合征女性体重、代谢参数及生殖结局的影响：一项前瞻性、随机、对照、开放标签临床试验

Effects of combined metformin and semaglutide therapy on body weight, metabolic parameters, and reproductive outcomes in overweight/obese women with polycystic ovary syndrome: a prospective, randomized, controlled, open-label clinical trial.

作者信息

Chen Haiyan, Lei Xiaohui, Yang Zhuoran, Xu Yuxin, Liu Dongfang, Wang Cong, Du Hu

机构信息

Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.

Department of Critical Care Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.

出版信息

Reprod Biol Endocrinol. 2025 Jul 26;23(1):108. doi: 10.1186/s12958-025-01447-3.

DOI:10.1186/s12958-025-01447-3

PMID:40713699

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12297736/

Abstract

OBJECTIVE

This study aimed to assess the effects of metformin (MET) monotherapy versus a combination of semaglutide and MET on weight, metabolism, reproductive function, and inflammatory markers in women with polycystic ovary syndrome (PCOS).

METHODS

A total of 100 overweight or obese women with PCOS diagnosed according to the Rotterdam criteria were randomly assigned to two groups: MET (1000 mg twice daily [BID] for 16 weeks) and combination therapy (COM) (1000 mg MET BID plus 1- mg semaglutide once weekly [QW] for 16 weeks). Primary outcomes, assessed at Week 0 and Week 16, included changes in anthropometric measures related to obesity, while the secondary outcomes included alterations in reproductive hormone levels, glucose and lipid metabolism, and C-reactive protein (CRP) levels, Between Weeks 16 and 40, all participants received metformin monotherapy (1000 mg BID) to evaluate pregnancy outcomes.

RESULT

A total of 80 participants (80%) completed the study. After 16 weeks of intervention, the COM group exhibited significantly greater reductions in body weight, BMI, and waist-to-hip ratio (WHR) compared to the MET group (all P < 0.01). The COM group experienced an average weight loss of 6.09 ± 3.34 kg, while the MET group lost only 2.25 ± 4.27 kg. The COM group also demonstrated greater improvements in testosterone (TEST), Chinese visceral adiposity index (CVAI), and CRP levels compared to the MET group. Additionally, the COM group showed higher rates of menstrual cycle recovery than the MET group. From weeks 16 to 40, the COM group demonstrated a significantly higher natural pregnancy rate than the MET group (35% vs. 15%, P < 0.05).

CONCLUSION

Compared to MET monotherapy, combination therapy with semaglutide and MET significantly reduced body weight, improved insulin resistance, decreased inflammatory markers, alleviated and menstrual irregularities and increased natural pregnancy rates in overweight/obese women with PCOS.

CLINICAL TRIAL REGISTRATION

chictr.org.cn ID: ChiCTR2400090908 (Registration time: 2024-10-15).

摘要

目的

本研究旨在评估二甲双胍（MET）单药治疗与司美格鲁肽联合MET治疗对多囊卵巢综合征（PCOS）女性体重、代谢、生殖功能及炎症标志物的影响。

方法

根据鹿特丹标准诊断的100例超重或肥胖PCOS女性被随机分为两组：MET组（每日两次，每次1000mg，共16周）和联合治疗组（COM组）（每日两次，每次1000mg MET加每周一次1mg司美格鲁肽，共16周）。在第0周和第16周评估的主要结局包括与肥胖相关的人体测量指标变化，次要结局包括生殖激素水平、糖脂代谢及C反应蛋白（CRP）水平的改变。在第16周至40周期间，所有参与者接受二甲双胍单药治疗（每日两次，每次1000mg）以评估妊娠结局。

结果

共80名参与者（80%）完成了研究。干预16周后，COM组的体重、BMI和腰臀比（WHR）下降幅度显著大于MET组（均P<0.01）。COM组平均体重减轻6.09±3.34kg，而MET组仅减轻2.25±4.27kg。COM组的睾酮（TEST）、中国内脏脂肪指数（CVAI）和CRP水平改善也大于MET组。此外，COM组月经周期恢复率高于MET组。在第16周至40周期间，COM组的自然妊娠率显著高于MET组（35%对15%，P<0.05）。