Empagliflozin vs Metformin in PCOS

Study Overview
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Brief Summary
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This a randomised open-label parallel study involving women with polycystic ovary syndrome (PCOS). The patients will be randomised either to metformin 1500mg or empagliflozin 25mg daily for three months. The aim of the study is to examine the effect of empagliflozin on hormonal, metabolic and cardiovascular risk markers and quality of life in women with PCOS.

Detailed Description
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Polycystic ovary syndrome (PCOS) is a very common condition in women that may present with irregular periods, excessive hair growth on the face and body, acne and cysts in the ovaries. PCOS is also associated with increased risk of problems later in life like diabetes, high cholesterol levels and heart disease. In this study, a medication named Empagliflozin will be tested. Empagliflozin belongs to a class of medicines known as SGLT-2 inhibitors. SGLT-2 stands for sodium glucose co-transporter 2. Empagliflozin, in simple terms, helps in reducing high blood glucose levels by increasing the amount of glucose passed in your urine. This medicine is usually used in patients with type 2 diabetes and has led to improved blood pressure and weight loss in addition to improving blood glucose levels. We want to give Empagliflozin to women with PCOS to see its effect on hormones related to PCOS and the risk factors for diabetes and heart disease. We will be comparing its effects to metformin (another drug for diabetes) which has already been used in PCOS with very good results.

Official Title
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The Effect of Empagliflozin Versus Metformin on Hormonal, Metabolic and Cardiovascular Risk Factors in Patients With Polycystic Ovary Syndrome (PCOS) - a Randomised Open-label Parallel Study.

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: Empagliflozin
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women, aged 18-45 years (inclusive), with confirmed diagnosis of PCOS based on Rotterdam criteria. Presence of both irregular periods and biochemical hyperandrogenaemia Body mass index ≥25 Negative pregnancy test during screening visit and agree to use barrier contraception during the study period. Exclusion Criteria: Non-classical 21-hydroxylase deficiency, hyperprolactinaemia, Cushing's disease and androgen-secreting tumours will be excluded by appropriate tests. Confirmed diagnosis of diabetes or pre-diabetes. Ongoing, inadequately controlled thyroid disorder (subjects on thyroid hormone replacement therapy must be on stable dose for at least 3 months before screening day) History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and in-situ carcinoma). History or plan of any form of gastrointestinal tract surgery. History of pancreatitis (Acute or Chronic). Any disorder which in the opinion of the investigator might jeopardize subject's safety. Subjects who are on any of the following medications within 3 months of recruitment: Metformin or other insulin-sensitizing medications (e.g., pioglitazone ) Hormonal contraceptives (e.g., birth control pills, hormone-releasing implants, etc.) Anti-androgens (e.g., spironolactone, flutamide, finasteride, etc.) Clomiphene citrate or estrogen modulators such as letrozole GnRH modulators such as leuprolide Minoxidil Female who is pregnant, breast feeding or intended to become pregnant or of child bearing potential not using adequate contraceptive methods. eGFR<60 Hypersensitivity to lactose Severe hepatic impairment (ALT >3 times ULN) Women with history of recurrent urinary tract infections. Haematocrit above the upper limit of normal range. Have been involved in another medicinal trial (CTIMP) within the past four weeks. Known hypersensitivity to the Investigational Medicinal Products or any of their excipients.

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: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Empagliflozin group<br>Each participant will receive empagliflozin 25mg daily for 3 months | Drug: Empagliflozin<br>* Each participant will receive empagliflozin 25mg daily for 3 months.<br>* Other names: Jardiance;|
| Active Comparator: Metformin group<br>Each participant will receive metformin 1500mg daily for 3 months | Drug: Metformin<br>* Each participant will receive metformin 1500mg daily for 3 months.<br>* Other names: Glucophage SR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial function as measured by RHI (reactive hyperaemia index). | Endothelial function as measured by RHI (reactive hyperaemia index) will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily | Three months treatment with either empagliflozin 25mg or metformin 1500mg daily | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory markers (hsCRP) | Inflammatory markers (hsCRP) will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily | Three months treatment with either empagliflozin 25mg or metformin 1500mg daily | 
| Insulin resistance as measured by HOMA (fasting glucose & insulin) | Insulin resistance as measured by HOMA (fasting glucose & insulin) will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily | Three months treatment with either empagliflozin 25mg or metformin 1500mg daily | 
| Body weight | Body weight will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily | Three months treatment with either empagliflozin 25mg or metformin 1500mg daily | 
| Blood pressure | Blood pressure will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily | Three months treatment with either empagliflozin 25mg or metformin 1500mg daily | 
| Lipid profile | Lipid profile will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily | Three months treatment with either empagliflozin 25mg or metformin 1500mg daily | 
| Hormonal parameters including free androgen index | Hormonal parameters including free androgen index will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily | Three months treatment with either empagliflozin 25mg or metformin 1500mg daily | 
| Endothelial function measured by microparticles | Endothelial function measured by microparticles will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily | Three months treatment with either empagliflozin 25mg or metformin 1500mg daily | 
| Quality of life Questionnaire | Quality of life will be assessed after three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily | Three months treatment with either empagliflozin 25mg or metformin S/R 1500mg daily |