Effects of GLP-1R agonist or co-cyprindiol, in combination with
metformin, on polycystic ovary syndrome in overweight women: A
Randomized Clinical Trial
Abstract
Objective: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 co-cyprindiol
(cyproterone acetate/ethinylestradiol, CPA/EE) + Met in overweight PCOS
women and identify potential biomarkers. 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) + Met
(1,500 mg/day) or GLP-1RA (liraglutide, 0.6-1.2 mg/day) + Met (1,500
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: Both interventions improved
menstrual cycle, polycystic ovaries, LH levels, and LH/FSH ratio;
meanwhile reduced the body weight, BMI, HbA1c, FBG, OGTT-30 min insulin,
IL-6 and TNF-α. Whereas, GLP-1RA + Met showed a more robust improvement
on HbA1c, HOMA-IR, lipid profiles, inflammatory parameters, and
ovulation. CPA/EE + Met was more effective in reducing
hyperandrogenemia. 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: CPA/EE+Met or
GLP-1RA + Met treatment improved reproductive functions and alleviated
metabolic disorders in overweight PCOS women. GLP-1RA + Met had a
superior improvement in metabolism and inflammation. The novel plasma
biomarkers PRDX6, FN1, and SERPINB9, might be indicators and targets for
PCOS treatment.