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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Polycystic Ovary Syndrome (PCOS)
• Intervention / Treatment: Drug: Metformin 1500 mg; Drug: Empagliflozin 25 mg; Drug: Linagliptin 10 mg

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 75
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Haidy M Sami, Master; Phone Number: +201015299642; Email: gs-haidy.sami@alexu.edu.eg
• Study Contact Backup: Name: Noha A Hamdy, PhD; Phone Number: +201005182151; Email: noha.alaaeldine@alexu.edu.eg

Study Locations

• Egypt
  • Alexandria, Egypt, 21521
    • Recruiting
    • Alexandria University
    • Contact: Ahmed I ElMallah, PhD; Phone Number: +201001708794; Email: ahmed.elmallah@alexu.edu.eg]
    • Principal Investigator: Noha A Hamdy, PhD
    • Principal Investigator: Hanan N Abdel Hafez, PhD
    • Principal Investigator: Haidi M Sami, Master

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Women diagnosed with PCOS according to National Institute of Health criteria.
2. Age: >18 <40 years.
3. Infertile women (primary or secondary infertility).

Exclusion Criteria:

1. Patients with history of diabetes mellitus (Type 1 or 2).
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.
3. Significantly elevated triglyceride levels (fasting triglyceride > 400 mg/dL)
4. Untreated or poorly controlled hypertension (sitting blood pressure > 160/95 mm Hg).
5. 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.
6. 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.
7. Presence of hypersensitivity to Empagliflozin or other Sodium/glucose cotransporter 2 (SGLT2) inhibitors (e.g. anaphylaxis, angioedema, exfoliative skin conditions).
8. Known hypersensitivity or contraindications to use dipeptidyl peptidase-4 (DPP-4) inhibitors (saxagliptin, linagliptin, sitagliptin…).
9. Use of Metformin, Thiazolidinediones, glucagon-like peptide-1 (GLP-1) receptor agonists, DPP-4 inhibitors, SGLT2 inhibitors stopped for at least 4 weeks.
10. Eating disorders (anorexia, bulimia) or gastrointestinal disorders.
11. Having a history of bariatric surgery.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Metformin arm (control group); Patients will receive Metformin (1500 mg orally/day) for 12 weeks .	Drug: Metformin 1500 mg; 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); Other Names: Metformin
Active Comparator: Empagliflozin arm; Patients will receive Empagliflozin (25 mg orally/day) for 12 weeks.	Drug: Empagliflozin 25 mg; 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); Other Names: Empagliflozin
Active Comparator: Linagliptin arm; Patients will receive Linagliptin (10 mg orally/day) for 12 weeks	Drug: Linagliptin 10 mg; 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); Other Names: Linagliptin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alexandria University
• Investigators: Study Chair: Hanan N Abdel Hafez, PhD, Professor of Obstetrics and Gynecology, Faculty of Medicine Mansoura University; Principal Investigator: Ahmed I ElMallah, PhD, Professor of Pharmacology and Therapeutics, Faculty of Pharmacy Alexandria University

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2021
• Primary Completion (Anticipated): July 1, 2022
• Study Completion (Anticipated): September 1, 2022

Study Registration Dates

• First Submitted: December 12, 2021
• First Submitted That Met QC Criteria: January 14, 2022
• First Posted (Actual): January 21, 2022

Study Record Updates

• Last Update Posted (Actual): January 21, 2022
• Last Update Submitted That Met QC Criteria: January 14, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: PCOS; Metformin; Empagliflozin; Linagliptin
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Polycystic Ovary Syndrome; Syndrome; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Empagliflozin; Linagliptin
• Other Study ID Numbers: 0201566

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No