SGLT2 Inhibitors in Treating Patients With PCOS

The Clinical Efficacy and Mechanism of SGLT2 Inhibitors Treating Polycystic Ovary Syndrome by Modulating the Nod-like Receptor Protein 3 Inflammasome

Chronic inflammation is the core of Polycystic ovary syndrome (PCOS), and obesity and overweight further exacerbate the level of inflammation in the peripheral circulation and ovarian tissue in PCOS patients. Metformin is a classic endocrine drug for the treatment of PCOS, but its clinical response rate is only about 40%. Our previous published study (Diabetes Obes Metab, 2022) observed that the new hypoglycemic drug SGLT-2 inhibitor can significantly improve the clinical symptoms of patients with insulin resistance PCOS, and the clinical efficacy is not inferior to metformin, but its specific mechanism of action is not clear. Recent studies have shown that SGLT-2 significantly attenuates the activation of the Nod-like receptor protein 3 (NLRP3) inflammasomes and the secretion of IL-1β in patients with type 2 diabetes mellitus at high risk of cardiovascular disease. Based on the above research background, this project will combine clinical research and mechanism exploration to solve the following two problems:

1. whether SGLT2 inhibitor can further improve the clinical efficacy of PCOS patients compared to metformin;
2. mechanistic studies further clarify whether SGLT2 inhibitors improve inflammatory symptoms by modulating NLRP3 inflammosomes in the treatment of polycystic ovary syndrome;

Study Overview

• Status: Completed
• Conditions: Polycystic Ovary Syndrome
• Intervention / Treatment: Drug: SGLT2 inhibitors; Drug: metformin

Detailed Description

This clinical study is a prospective, single-center, randomized (1:1) controlled clinical study. The enrollment population is overweight or obese PCOS patients. After signing the informed consent form, patients who meet the inclusion/exclusion criteria will be randomly assigned to the experimental and control groups for treatment in a 1:1 ratio, for a total of 80 patients enrolled.

Subjects randomized to the trial group will receive SGLT-2 inhibitors for 24 weeks.

Participants randomised to control will receive metformin for 24 weeks.

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200072
      • Shanghai Tenth People's Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Female aged 18-45
• Meet Rotterdam criteria
• BMI≥20kg/m2

Exclusion Criteria:

• Treatment with any additional medications that might impede the trial, including GLP-1 RAs, metformin, pioglitazone, contraceptives, or traditional Chinese medicine within the past 3 months
• Pregnancy or lactation
• Mental illness
• Malignant tumors
• Chronic kidney disease or severe liver dysfunction
• Inflammatory bowel disease
• Involvement in other research programs within the past 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SGLT2 inhibitors; Intervention with henggliflozin (10mg qd) for 6 months	Drug: SGLT2 inhibitors; Sodium-glucose cotransporters inhibitors (SGLT2i) are novel hypoglycemic drugs with unique hypoglycemic mechanisms, which are completely independent of islet β-cell function or insulin sensitivity. Previous studies have shown that SGLT2i may improve IR by inhibiting glucotoxicity, reducing body weight, reducing inflammation, improving islet β-cell function, and reducing oxidative stress.
Placebo Comparator: metformin; Intervention with metformin (500mg bid) for 6 months	Drug: metformin; Metformin is a classic drug for the treatment of polycystic ovary syndrome, which can improve the degree of insulin resistance in PCOS patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Menstrual cycles	annual number of menstrual cycles	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HOMA-IR	Homeostatic model assessment insulin resistance index	6 months
LH	luteinizing hormone	6 months
FSH	follicle-stimulating hormone	6 months
PRL	prolactin	6 months
E2	estradiol	6 months
P	progesterone	6 months
TT	total testosterone	6 months
AMH	antimullerian hormone antimullerian hormone antimullerian hormone antimullerian hormone	6 months
NLRP3	serum Nod-like receptor protein 3	6 months
IL-1β	serum Interleukin-1 beta	6 months
IL-18	serum Interleukin-18	6 months

Collaborators and Investigators

• Sponsor: Shanghai 10th People's Hospital
• Investigators: Principal Investigator: Manna Zhang, PhD, Shanghai 10th People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2023
• Primary Completion (Actual): June 30, 2025
• Study Completion (Actual): June 30, 2025

Study Registration Dates

• First Submitted: July 21, 2023
• First Submitted That Met QC Criteria: July 21, 2023
• First Posted (Actual): August 1, 2023

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: June 1, 2025

More Information

Terms related to this study

• 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Organic Chemicals; Pharmacologic Actions; Chemical Actions and Uses; Biguanides; Guanidines; Amidines; Sodium-Glucose Transporter 2 Inhibitors; Metformin
• Other Study ID Numbers: SGLT2i in PCOS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No