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

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...

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Main Authors: Haiyan Chen, Xiaohui Lei, Zhuoran Yang, Yuxin Xu, Dongfang Liu, Cong Wang, Hu Du
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Reproductive Biology and Endocrinology
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Online Access:https://doi.org/10.1186/s12958-025-01447-3
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author Haiyan Chen
Xiaohui Lei
Zhuoran Yang
Yuxin Xu
Dongfang Liu
Cong Wang
Hu Du
author_facet Haiyan Chen
Xiaohui Lei
Zhuoran Yang
Yuxin Xu
Dongfang Liu
Cong Wang
Hu Du
author_sort Haiyan Chen
collection DOAJ
description 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).
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spelling doaj-art-e9e0914b4e3b4c6f8e5c37ab8f6358c92025-08-20T04:02:45ZengBMCReproductive Biology and Endocrinology1477-78272025-07-0123111210.1186/s12958-025-01447-3Effects 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 trialHaiyan Chen0Xiaohui Lei1Zhuoran Yang2Yuxin Xu3Dongfang Liu4Cong Wang5Hu Du6Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Endocrinology, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Endocrinology, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Endocrinology, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Endocrinology, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Endocrinology, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Critical Care Medicine, The Second Affiliated Hospital of Chongqing Medical UniversityAbstract 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).https://doi.org/10.1186/s12958-025-01447-3SemaglutidePolycystic ovary syndromeMetforminPregnancy outcomes
spellingShingle Haiyan Chen
Xiaohui Lei
Zhuoran Yang
Yuxin Xu
Dongfang Liu
Cong Wang
Hu Du
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
Reproductive Biology and Endocrinology
Semaglutide
Polycystic ovary syndrome
Metformin
Pregnancy outcomes
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Semaglutide
Polycystic ovary syndrome
Metformin
Pregnancy outcomes
url https://doi.org/10.1186/s12958-025-01447-3
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