Effects and plasma proteomic analysis of GLP-1RA versus CPA/EE, in combination with metformin, on overweight PCOS women: a randomized controlled trial

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Abstract

Purpose

Polycystic ovary syndrome (PCOS) is characterized by reproductive dysfunctions and metabolic disorders. This study aims to compare the therapeutic effectiveness of glucagon-like peptide-1 receptor agonist (GLP-1RA) + Metformin (Met) versus cyproterone acetate/ethinylestradiol (CPA/EE) + Met in overweight PCOS women and identify potential proteomic biomarkers of disease risk in women with PCOS.

Methods

In this prospective, open-label randomized controlled trial, we recruited 60 overweight PCOS women into two groups at a 1:1 ratio to receive CPA/EE (2 mg/day: 2 mg cyproterone acetate and 35-μg ethinylestradiol,) +Met (1500 mg/day) or GLP-1 RA (liraglutide, 1.2–1.8 mg/day) +Met (1500 mg/day) for 12 weeks. The clinical effectiveness and adverse effects were evaluated, followed by plasma proteomic analysis and verification of critical biomarkers by ELISA.

Results

Eighty(80%) patients completed the study. Both interventions improved menstrual cycle, polycystic ovaries, LH(luteinizing hormone) and HbA1c(hemoglobin A1c) levels after the 12-week treatment. GLP-1RA + Met was more effective than CPA/EE + Met in reducing body weight, BMI (Body Mass Index), and waist circumference, FBG(fasting blood glucose), AUCI(area under curve of insulin),TC (Total Cholesterol), IL-6(Interleukin-6) and improving insulin sensitivity, and ovulation in overweight women with PCOS, with acceptable short-term side effects. CPA/EE + Met was more effective in improving hyperandrogenemia, including T(total testosterone), LH, LH/FSH(Luteinizing hormone/follicle-stimulating hormone), SHBG(sex hormone-binding globulin) and FAI (free androgen index). By contract, GLP-1RA+Met group only improved LH. Plasma proteomic analysis revealed that the interventions altered proteins involved in reactive oxygen species detoxification (PRDX6, GSTO1, GSTP1, GSTM2), platelet degranulation (FN1), and the immune response (SERPINB9).

Conclusions

Both CPA/EE+Met and GLP-1RA + Met treatment improved reproductive functions in overweight PCOS women. GLP-1RA + Met was more effective than CPA/EE + Met in reducing body weight, BMI, and waist, and improving metabolism, and ovulation in overweight women with PCOS, with acceptable short-term side effects. CPA/EE + Met was more effective in reducing hyperandrogenemia. The novel plasma biomarkers PRDX6, FN1, and SERPINB9, might be indicators and targets for PCOS treatment.

Trial registration ClinicalTials.gov Trial No:

NCT03151005. Registered 12 May, 2017, https://clinicaltrials.gov/ct2/show/NCT03151005.

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Most cited references 44

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Author and article information

Contributors

Zheng Sun: zheng.sun@bcm.edu

Hongting Zheng: fnf7703@hotmail.com

Min Long:

ORCID: http://orcid.org/0000-0003-1071-8131

longmin_casper@163.com

Journal

Journal ID (nlm-ta): Endocrine

Journal ID (iso-abbrev): Endocrine

Title: Endocrine

Publisher: Springer US (New York )

ISSN (Print): 1355-008X

ISSN (Electronic): 1559-0100

Publication date (Electronic): 31 August 2023

Publication date PMC-release: 31 August 2023

Publication date (Print): 2024

Volume: 83

Issue: 1

Pages: 227-241

Affiliations

[1 ]GRID grid.410570.7, ISNI 0000 0004 1760 6682, Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, , Army Medical University, ; Chongqing, 400037 China

[2 ]Department of Endocrinology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210016 China

[3 ]GRID grid.9227.e, ISNI 0000000119573309, Key Laboratory of Genetic Network Biology, Collaborative Innovation Center of Genetics and Development, Institute of Genetics and Developmental Biology, , Chinese Academy of Sciences, ; 100101 Beijing, China

[4 ]Univeristy of Chinese Academy of Sciences, ( https://ror.org/05qbk4x57) 100049 Beijing, China

[5 ]GRID grid.410570.7, ISNI 0000 0004 1760 6682, Department of Endocrinology, Southwest Hospital, , Army Medical University (Third Military Medical University), ; Chongqing, 400038 China

[6 ]Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine, ( https://ror.org/02pttbw34) Houston, TX USA

Author information

Min Long http://orcid.org/0000-0003-1071-8131

Article

Publisher ID: 3487

DOI: 10.1007/s12020-023-03487-4

PMC ID: 10806039

PubMed ID: 37653215

SO-VID: 2a07e199-14c0-4798-940e-f7d42b6a79ad

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 10 April 2023

Date accepted : 9 August 2023

Funding

Funded by: FundRef https://doi.org/10.13039/, Chongqing Natural Science Foundation;

Award ID: No.cstc2020jcyj-jqx0017

Award Recipient : Mingyu Liao Min Long

Funded by: FundRef https://doi.org/10.13039/http://dx.doi.org/10.13039/501100014219, National Science Fund for Distinguished Young Scholars;

Award ID: No. 81925007

Award Recipient : Hongting Zheng

Custom metadata

ScienceOpen disciplines: Endocrinology & Diabetes

Keywords: pcos (polycystic ovary syndrome),glucagon-like peptide-1 receptor agonist (glp-1 ra),metformin,proteomics analysis

Data availability:

ScienceOpen disciplines: Endocrinology & Diabetes

Keywords: pcos (polycystic ovary syndrome), glucagon-like peptide-1 receptor agonist (glp-1 ra), metformin, proteomics analysis

Effects and plasma proteomic analysis of GLP-1RA versus CPA/EE, in combination with metformin, on overweight PCOS women: a randomized controlled trial

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Trial registration ClinicalTials.gov Trial No:

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Journal of the ASEAN Federation of Endocrine Societies

Most cited references 44

Cytoscape: a software environment for integrated models of biomolecular interaction networks.

limma powers differential expression analyses for RNA-sequencing and microarray studies

Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.

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