Efficacy of Empagliflozin or Linagliptin as an Alternative to Metformin for Treatment of Polycystic Ovary Syndrome

Study Overview
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Brief Summary
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The study aims to compare the efficacy of Empagliflozin or Linagliptin as an alternative to Metformin for treatment of non-diabetic patients with polycystic ovary syndrome (PCOS).

Detailed Description
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Patients with polycystic ovary syndrome will be randomized to three arms: Metformin (standard care) Empagliflozin or Linagliptin Resolution of the syndrome in addition to normalization of sex hormones, metabolic and inflammatory parameters will be tested

Official Title
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A Comparative Clinical Study Evaluating the Efficacy of Empagliflozin or Linagliptin as an Alternative to Metformin for Treatment of Polycystic Ovary Syndrome in Egyptian Women

Conditions
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Polycystic Ovary Syndrome (PCOS)

Intervention / Treatment
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* Drug: Empagliflozin 25 mg
* Drug: Linagliptin 10 mg
* Drug: Metformin 1500 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women diagnosed with PCOS according to National Institute of Health criteria. Age: >18 <40 years. Infertile women (primary or secondary infertility). Exclusion Criteria: Patients with history of diabetes mellitus (Type 1 or 2). Patients with liver or renal dysfunction; inflammatory diseases; autoimmune disease; cancer, acute cardiovascular event within last three months and uncontrolled endocrine or metabolic disease. Significantly elevated triglyceride levels (fasting triglyceride > 400 mg/dL) Untreated or poorly controlled hypertension (sitting blood pressure > 160/95 mm Hg). Use of hormonal medications, lipid-lowering (statins, etc.), anti-obesity drugs or weight loss medications (prescription or OTC) and medications known to exacerbate glucose tolerance (such as isotretinoin, hormonal contraceptives, glucocorticoids, anabolic steroids) stopped for at least 8 weeks. Use of anti-androgens that act peripherally to reduce hirsutism such as 5-alpha reductase inhibitors stopped for at least 4 weeks. Patients at risk for volume depletion due to co-existing conditions or concomitant medications, such as loop diuretics should have careful monitoring of their volume status. Presence of hypersensitivity to Empagliflozin or other Sodium/glucose cotransporter 2 (SGLT2) inhibitors (e.g. anaphylaxis, angioedema, exfoliative skin conditions). Known hypersensitivity or contraindications to use dipeptidyl peptidase-4 (DPP-4) inhibitors (saxagliptin, linagliptin, sitagliptin…). Use of Metformin, Thiazolidinediones, glucagon-like peptide-1 (GLP-1) receptor agonists, DPP-4 inhibitors, SGLT2 inhibitors stopped for at least 4 weeks. Eating disorders (anorexia, bulimia) or gastrointestinal disorders. Having a history of bariatric surgery.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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 |
| --- | --- |
| Active Comparator: Metformin arm (control group)<br>Patients will receive Metformin (1500 mg orally/day) for 12 weeks . | Drug: Metformin 1500 mg<br>* This study is to compare the efficacy of Empagliflozin or Linagliptin as an alternative to Metformin for treatment of non-diabetic patients with polycystic ovary syndrome (PCOS)<br>* Other names: Metformin;|
| Active Comparator: Empagliflozin arm<br>Patients will receive Empagliflozin (25 mg orally/day) for 12 weeks. | Drug: Empagliflozin 25 mg<br>* This study is to compare the efficacy of Empagliflozin or Linagliptin as an alternative to Metformin for treatment of non-diabetic patients with polycystic ovary syndrome (PCOS)<br>* Other names: Empagliflozin;|
| Active Comparator: Linagliptin arm<br>Patients will receive Linagliptin (10 mg orally/day) for 12 weeks | Drug: Linagliptin 10 mg<br>* This study is to compare the efficacy of Empagliflozin or Linagliptin as an alternative to Metformin for treatment of non-diabetic patients with polycystic ovary syndrome (PCOS)<br>* Other names: Linagliptin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fertility parameters | [luteinizing hormone (LH) | 3-6 months | 
| Follicle-stimulating hormone | FSH | 3-6 months | 
| Free androgen index | total testosterone & sex hormone binding globulin (SHBG) | 3-6 months | 
| Transvaginal ultrasonography | disappearance of PCOS | 3-6 months | 
| Menstrual diaries | regulate menses cycles | 3-6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolic parameters | Fasting blood glucose level | 3-6 months | 
| Lipid profile (metabolic parameters) | Total cholesterol, Low density lipoprotein (LDL), very low density lipoprotein (VLDL), high density lipoprotein (HDL), triglycerides (TG), atherogenic index I, II | 3-6 months | 
| Inflammatory indices | Interleukin 6 or Toll Like receptor 2 | 3-6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PCOS, Empagliflozin, Linagliptin, Metformin