Efficacy of a GLP-1/FGF21 Dual Agonist for Treating PCOS

Inclusion Criteria:

• Age between 18 and 40 years.
• Female.
• No plan for pregnancy from the time of signing the informed consent until 2 months after the last dose of study drug, and willingness to use study-approved contraceptive methods during this period.

• Fulfillment of at least two of the diagnostic criteria for PCOS according to the 2023 International Guideline, including:

  1. Irregular menstrual cycles:

     1-3 years after menarche: cycle length <21 days or >45 days; ≥3 years after menarche to perimenopause: cycle length <21 days or >35 days, or fewer than 8 menstrual cycles per year; ≥1 year after menarche: any cycle >90 days;

  2. Polycystic ovarian morphology: at least one ovary with ≥20 antral follicles (diameter <10 mm), confirmed by transvaginal or transrectal pelvic ultrasonography;
  3. Hyperandrogenism: biochemical hyperandrogenism (total testosterone >1.67 nmol/L) or clinical hyperandrogenism (modified Ferriman-Gallwey [mFG] score >4).

Exclusion Criteria:

• Use of hormonal contraceptives within 2 months prior to screening.
• History of acute or chronic pancreatitis or pancreatic injury.
• Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2A or 2B.
• History of type 1 or type 2 diabetes mellitus.
• Presence of other endocrine disorders that may cause polycystic ovarian morphology, such as 21-hydroxylase deficiency, pituitary prolactinoma, hypothyroidism, or Cushing's syndrome.
• Current use of other medications known to affect reproductive function, with discontinuation less than 2 months prior to screening, including GnRH agonists or antagonists, anti-androgens, and gonadotropins.
• Current use of other medications that may affect metabolism, with discontinuation less than 1 month prior to screening, including metformin, thiazolidinediones, and SGLT2 inhibitors.
• History of bariatric surgery within the past 12 months.
• Treatment with GLP-1 receptor agonists within the past 12 months.
• Pregnancy or lactation.
• Presence of other serious diseases of major organs such as the heart, liver, or kidney, or any malignancy.
• Any other condition that, in the investigator's opinion, may interfere with the evaluation of efficacy or safety or render the participant unsuitable for this study.