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

A Preliminary Study to Explore the Efficacy of a GLP-1/FGF21 Dual Agonist (HEC88473) in Patients With Polycystic Ovary Syndrome (PCOS)

Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine and metabolic disorder among women of reproductive age. It is characterized by oligo-ovulation or anovulation, clinical and/or biochemical hyperandrogenism, and polycystic ovarian morphology. In addition, PCOS is frequently accompanied by multiple metabolic abnormalities, including insulin resistance, obesity, impaired glucose tolerance, and dyslipidemia. Clinical studies have demonstrated that treatment with glucagon-like peptide-1 receptor agonists (GLP-1RAs) in women with PCOS results in significant weight reduction, decreased free testosterone levels, improvement in menstrual regularity, and increased clinical pregnancy rates. Fibroblast growth factor 21 (FGF21) has been shown to enhance insulin sensitivity, promote fatty acid oxidation, and improve lipid distribution.

HEC88473 is a novel long-acting dual agonist targeting both the glucagon-like peptide-1 (GLP-1) receptor and the fibroblast growth factor 21 (FGF21) receptor. This study is initiated to evaluate the clinical efficacy of HEC88473 in women with PCOS and to explore its potential as a new therapeutic option for the management of PCOS.

Study Overview

• Status: Recruiting
• Conditions: PCOS (Polycystic Ovary Syndrome)
• Intervention / Treatment: Drug: GLP-1/FGF21 dual agonist (HEC88473)

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jingjing JIANG, MD, PhD; Phone Number: 86-021-64041990; Email: jiang.jingjing@zs-hospital.sh.cn

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 201508
      • Recruiting
      • Zhongshan Hospital, Fudan University
      • Contact: Jingjing JIANG, MD, PhD; Phone Number: 86-021-64041990; Email: jiang.jingjing@zs-hospital.sh.cn
      • Principal Investigator: Jingjing JIANG, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HEC88473 Treatment in Women With PCOS; To evaluate the longitudinal changes in androgen metabolism in women with polycystic ovary syndrome (PCOS) during treatment with the GLP-1/FGF21 dual agonist HEC88473.	Drug: GLP-1/FGF21 dual agonist (HEC88473); GLP-1/FGF21 dual agonist (HEC88473) will be administered by subcutaneous injection once weekly. The starting dose is 15 mg for 3 consecutive weeks. If well tolerated, the dose will be escalated to 30 mg for an additional 3 weeks, followed by further escalation to 45 mg for 18 weeks, provided tolerability is maintained.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Free Androgen Index Over 24 Weeks of Treatment	Longitudinal changes in free androgen index from baseline at each scheduled follow-up visit during the 24-week treatment period.	Baseline to Week 24 (assessed at scheduled follow-up visits).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Number of Spontaneous Menstrual Cycles During the 24-Week Treatment Period Compared With the 24-Week Pre-treatment Period	Comparison of the number of spontaneous menstrual cycles during the 24-week intervention period with those during the 24-week period prior to treatment initiation.	24 weeks before treatment initiation to 24 weeks after treatment initiation.
Change From Baseline in Bilateral Antral Follicle Count (Diameter <10 mm) at Week 24	Change from baseline in the total number of antral follicles with a diameter <10 mm in both ovaries after 24 weeks of treatment.	Baseline to Week 24.
Change From Baseline in Bilateral Ovarian Volume at Week 24	Change from baseline in the total ovarian volume of both ovaries after 24 weeks of treatment.	Baseline to Week 24.
Change From Baseline in Serum AMH at Week 24	Change from baseline in serum levels of anti-Müllerian hormone (AMH) after 24 weeks of treatment.	Baseline to Week 24.
Change From Baseline in Serum Total Testosterone at Week 24	Change from baseline in serum levels of total testosterone after 24 weeks of treatment.	Baseline to Week 24.
Change From Baseline in Serum DHEA-S at Week 24	Change from baseline in serum levels of dehydroepiandrosterone sulfate (DHEA-S) after 24 weeks of treatment.	Baseline to Week 24.
Change From Baseline in Serum SHBG at Week 24	Change from baseline in serum levels of sex hormone-binding globulin (SHBG) after 24 weeks of treatment.	Baseline to Week 24.
Change From Baseline in HOMA IR Index at Week 24	Change from baseline in insulin resistance assessed by the HOMA Insulin Resistance index (calculated from fasting plasma glucose in mmol/L × fasting serum insulin in μU/mL/22.5) after 24 weeks of treatment.	Baseline to Week 24.
Change From Baseline in Lipid Profile at Week 24	Change from baseline in serum lipid profile after 24 weeks of treatment.	Baseline to Week 24.
Change From Baseline in Body Weight at Week 24	Change from baseline in body weight after 24 weeks of treatment.	Baseline to Week 24.
Change From Baseline in Waist Circumference at Week 24	Change from baseline in waist circumference after 24 weeks of treatment.	Baseline to Week 24.
Change From Baseline in Quality of Life Assessed by SF-36 at Week 24	Change from baseline in quality of life evaluated using the Short Form-36 (SF-36) after 24 weeks of treatment.	Baseline to Week 24.
Change From Baseline in Quality of Life Assessed by PCOSQ at Week 24	Change from baseline in quality of life evaluated using the Polycystic Ovary Syndrome Questionnaire (PCOSQ) after 24 weeks of treatment.	Baseline to Week 24.
Incidence and Severity of Adverse Events During the 24-Week Treatment Period	Assessment of the incidence, type, and severity of adverse events occurring during the 24-week treatment period.	Baseline to Week 24.

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: May 4, 2026
• First Submitted That Met QC Criteria: May 25, 2026
• First Posted (Actual): May 29, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 25, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: PCOS; GLP-1/FGF21 dual agonist
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Ovarian Cysts; Cysts; Polycystic Ovary Syndrome
• Other Study ID Numbers: B2025-709R

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: After publication.
• IPD Sharing Access Criteria: IPD and supporting information will be available to researchers upon reasonable request (e.g., with a practical and meaningful research proposal).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No