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 metformin plus SGLT2 inhibitor can further improve the clinical efficacy of PCOS patients compared to metformin plus placebo;
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: Not yet recruiting
• Conditions: Polycystic Ovary Syndrome
• Intervention / Treatment: Drug: SGLT2 inhibitors combined with metformin; Drug: Placebo combined with 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 72 patients enrolled.

Subjects randomized to the trial group will receive SGLT-2 inhibitors plus metformin for 12 weeks.

Participants randomised to control will receive placebo plus metformin for 12 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Female aged 18-45
• Meet Rotterdam criteria
• Insulin resistance

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 combined with metformin; Intervention with henggliflozin (5mg qd) and metformin (500mg bid) for 3 months	Drug: SGLT2 inhibitors combined with metformin; 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.; Other Names: Henggliflozin combined with metformin
Placebo Comparator: Placebo combined with metformin; Intervention with placebo (qd) and metformin (500mg bid) for 3 months	Drug: Placebo combined with 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
HOMA-IR	Homeostatic model assessment insulin resistance index	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Menstrual cycles	annual number of menstrual cycles	3 months
NLRP3	Nod-like receptor protein 3	3 months
IL-1β	Interleukin-1 beta	3 months
IL-18	Interleukin-18	3 months
LH	luteinizing hormone	3 months
FSH	follicle-stimulating hormone	3 months
PRL	prolactin	3 months
E2	estradiol	3 months
P	progesterone	3 months
TT	total testosterone	3 months

Collaborators and Investigators

• Sponsor: Shanghai 10th People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 15, 2023
• Primary Completion (Estimated): December 15, 2024
• Study Completion (Estimated): March 15, 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): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 21, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Polycystic Ovary Syndrome; Syndrome; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Metformin; Sodium-Glucose Transporter 2 Inhibitors
• Other Study ID Numbers: SGLT2i NLRP3 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