SGLT2 Inhibitors in Patients With PCOS

Study Overview
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Brief Summary
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Polycystic ovary syndrome (PCOS) is a common endocrine disorder, with a prevalence of 5% to 15% in premenopausal women. Patients with PCOS presents as abnormal menstruation, ovulation disorders and/or hyperandrogenemia, and often accompanied by insulin resistance and other metabolic abnormalities. Metformin has been clarified as an option in patients with PCOS. However, the clinical responses to metformin are limited and different. Sodium glucose co-transporter 2 (SGLT2) inhibitors are novel drugs for the treatment of type 2 diabetes, with weight loss, reducing insulin resistance and cardiovascular benefits. Limited data is available on the efficacy of SGLT2 inhibitors in patients with PCOS.

Detailed Description
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This clinical study aims to determine the safety and efficacy of canagliflozin vs metformin in Polycystic Ovary Syndrome (PCOS) patients with insulin resistance (IR). Methods: A single center, prospective, randomized open-label study (ratio 1:1), non-inferiority trial was conducted in the department of endocrinology, Shanghai Tenth People's Hospital between July 2019 and April 2021. PCOS women aged 18-45 years with IR were enrolled and randomly assigned to either canagliflozin 100 mg (n = 33) or metformin 1500-2000 mg (n = 35) daily for 12 weeks. The primary outcome was changes in HOMA-IR after 12 weeks treatment. The secondary outcomes included changes in anthropometric, menstrual frequency, sex hormone and metabolic parameters.

Official Title
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The Efficacy of Canagliflozin Versus Metformin in Women With Polycystic Ovary Syndrome: A Randomized, Open Label Trial

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: SGLT2 inhibitors
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Fmale aged 18- 45; Meet Rotterdam criteria; Insulin Rsistance Exclusion Criteria: Women who are pregnant or have a pregnancy plan within six months; ·Congenital adrenocortical hyperplasia; Hyperprolactinemia; Hyperthyroidism or hypothyroidism; Abnormal liver function (≥ 3 times of the upper limit of normal range); Abnormal renal function (GFR<60ml/min/1.73m2); Adrenal or ovarian tumors secreting androgens; Used contraceptives, metformin, GLP-1RA, SGLT2I, pioglitazone and contraceptives in the last 3 month.

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 group<br>Intervention with SGLT2 inhibitors (100mg/d) for 3 months | Drug: SGLT2 inhibitors<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: Canagliflozin tablets or Glucophage;|
| Active Comparator: Metformin group<br>Intervention with metformin (1500-2000mg/d) for 3 months | Drug: 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 |
| --- | --- | --- |
| WHR | Waist/hip Ratio | 3 months | 
| WC | Waist Circumference (cm） | 3 months | 
| HC | Hip Circumference（cm） | 3 months | 
| Menstrual cycles | annual number of menstrual cycles | 3 months | 
| FBG | fasting blood-glucose in mmol/L | 3 months | 
| PBG | postprandial blood-glucose in mmol/L | 3 months | 
| FINS | fasting serum insulin in mU/L | 3 months | 
| PINS | Postprandial insulin in mU/L | 3 months | 
| ALT | alanine aminotransferase in U/L | 3 months | 
| AST | Aspartate aminotransferase in U/L | 3 months | 
| UA | Uric acid in umol/L | 3 months | 
| CR | Creatinine in umol/L | 3 months | 
| LDL-c | low-density lipoprotein cholesterol in mmol/L | 3 months | 
| HDL-c | high-density lipoprotein cholesterol in mmol/L | 3 months | 
| TC | Total Cholesterol in mmol/L | 3 months | 
| TG | Triglyceride in mmol/L | 3 months | 
| TT | total testosterone in nmol/L | 3 months | 
| LH | Luteinizing hormone in IU/L | 3 months | 
| FSH | follicle-stimulating hormone in IU/L） | 3 months | 
| E2 | Estradiol in pmol/L、PRL(Prolactin in uIU/ml) | 3 months | 
| PRL | Prolactin in uIU/ml | 3 months | 
| Metabonomics | the change of Metabonomics after the treatment | 3 months | 
| Ferriman-Gallwey score | Ferriman-Gallwey score、acne, male pattern baldness | 3 months | 
| acne score | male pattern baldness | 3 months | 
| male pattern baldness | male pattern baldness | 3 months | 
| HOMA- ISI | Homeostatic model assessment insulin sensitivity index | 3 months | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Adverse events and Safety data in two treatment groups. | 3 months | 
| BMI | body mass index in kg/m^2 | 3 months | 
| SHBG | sex hormone binding globulin in nmol/L | 3 months | 
| FT | Free testosterone in pg/ml | 3 months | 
| DHEAS | Dehydroepiandrosterone Sulfate in ug/dl | 3 months | 
| AD | Androstenedione in ng/ml | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polycystic ovary syndrome (PCOS);, Insulin resistance (IR), Sodium-glucose co-transporter-2 inhibitors (SGLT-2i), Canagliflozin