ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Reproduction
This article is part of the Research TopicThe Influence of Vaginal, Urinary, and Intestinal Microbiomes on Gynecological DiseasesView all articles
Combination Metformin and Liraglutide in PCOS: Clinical Efficacy in Women and Preclinical Insights from Gut Microbiome Modulation in Rats
Provisionally accepted
- Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Background: Metformin and liraglutide have been gradually used in the treatment of polycystic ovary syndrome (PCOS) due to their metabolic benefits, but also with some adverse reactions. Evidence suggests that gut microbiota imbalance plays an important role in the pathogenesis of PCOS. This study comprised a clinical trial to evaluate the efficacy of metformin, liraglutide, and their combination in PCOS women, and a parallel animal experiment to explore the potential involvement of gut microbiota. Methods: In an open-label randomized controlled trial, sixty overweight/obese women with PCOS were randomized to: the MET group received oral metformin (0.85 g twice daily; n=20), the LIRA group received subcutaneous liraglutide (1.2 mg once daily; n=20), and the COM group received both treatments (n=20) for 12 weeks. In a separate animal study, female Sprague-Dawley rats were divided into five groups: (1) PCOS model group (letrozole 1 mg/kg orally); (2) MET group (letrozole + metformin 200 mg/kg orally); (3) LIRA group (letrozole + liraglutide 0.2 mg/kg subcutaneously); (4) COM group (letrozole + metformin + liraglutide at above doses); and (5) healthy controls (no treatment). All treatments lasted 4 weeks. Results: In the clinical trial, women in MET, LIRA, and COM groups showed significant reductions in body weight, blood glucose, blood lipid, and the LH/FSH ratio. Notably, body weight, BMI, visceral fat area, and body fat percentage decreased more significantly in the COM group than in the MET group (P<0.05). Compared with the MET group, the COM group was more effective in reducing free testosterone (P =0.01). In the animal experiment, the body weight, estrus cycle, and ovarian morphology of rats in the COM group were significantly improved. Letrozole-induced PCOS rats showed intestinal flora disorder, which was improved by metformin, liraglutide, and their combination
Keywords: Polycystic Ovary Syndrome, Metformin, liraglutide, Metabolism, endocrine, Gut Microbiota
Received: 05 Apr 2025; Accepted: 10 Nov 2025.
Copyright: © 2025 Long, Fang, Li, Li, Wang, Wang, Zhang and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Ling Zhang, zhanglingxh@hust.edu.cn
Yi Liu, liqun1994@hust.edu.cn
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