SGLT2 Inhibitors in Treating Patients With PCOS

Study Overview
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Brief Summary
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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: whether metformin plus SGLT2 inhibitor can further improve the clinical efficacy of PCOS patients compared to metformin plus placebo; mechanistic studies further clarify whether SGLT2 inhibitors improve inflammatory symptoms by modulating NLRP3 inflammosomes in the treatment of polycystic ovary syndrome;

Detailed Description
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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.

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

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: SGLT2 inhibitors combined with metformin
* Drug: Placebo combined with metformin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SGLT2 inhibitors combined with metformin<br>Intervention with henggliflozin (5mg qd) and metformin (500mg bid) for 3 months | Drug: SGLT2 inhibitors combined with metformin<br>* 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.<br>* Other names: Henggliflozin combined with metformin;|
| Placebo Comparator: Placebo combined with metformin<br>Intervention with placebo (qd) and metformin (500mg bid) for 3 months | Drug: Placebo combined with metformin<br>* Metformin is a classic drug for the treatment of polycystic ovary syndrome, which can improve the degree of insulin resistance in PCOS patients.<br>|

What is the study measuring?
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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 |