Efficacy of Dapagliflozin Versus Metformin in Polycystic Ovary Syndrome

Efficacy of Dapagliflozin Versus Metformin in Polycystic Ovary Syndrome: A Prospective Comparative Randomized Blinded Trial.

In PCOS (Polycystic Ovary Syndrome), studies have found impaired incretin secretion and activity, particularly in overweight/obese individuals.

Conflicting results exist regarding glucagon-like peptide-1(GLP-1) levels in PCOS patients, with studies reporting reduced, normal, or increased levels. Incretin-based therapy has been suggested as a potential treatment to reverse prediabetes risk by preserving β-cell function in patients with impaired fasting glucose(IFG and impaired glucose tolerance(IGT). The study aims to compare the efficacy of Dapagliflozin to Metformin for the treatment of non-diabetic patients with polycystic ovary syndrome (PCOS).

Study Overview

• Status: Recruiting
• Conditions: Polycystic Ovary Syndrome
• Intervention / Treatment: Drug: Dapagliflozin; Drug: Metformin

Detailed Description

Incretins such as glucagon-like peptide-1(GLP-1) are gut hormones secreted after meals that enhance insulin secretion and help maintain glucose homeostasis.They also reduce hepatic glucagon release, slow gastric emptying, and suppress appetite, aiding in weight control and glycemic management.In PCOS (Polycystic Ovary Syndrome), studies have found impaired incretin secretion and activity, particularly in overweight/obese individuals.Conflicting results exist regarding GLP-1 levels in PCOS patients, with studies reporting reduced, normal, or increased levels.After an oral glucose tolerance test, increased GIP and lower GLP-1 concentrations have been observed in women with PCOS.

Reduced GLP-1 levels are also associated with impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), which are early indicators of prediabetes and potential progression to Type 2 Diabetes Mellitus.Incretin-based therapy has been suggested as a potential treatment to reverse prediabetes risk by preserving β-cell function in patients with IFG and IGT. The study aims to compare the efficacy of Dapagliflozin to Metformin for treatment of non-diabetic patients with polycystic ovary syndrome (PCOS).

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Nouran Omar; Phone Number: +2 01006526452; Email: nomar@fue.edu.eg

Study Locations

• Egypt
  • Giza, Egypt
    • Recruiting
    • October 6 University Hospital
    • Contact: Ahmed Hussein; Phone Number: +2 01001749605

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women diagnosed with PCOS according to Rotterdam 2003 criteria 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.
• 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 dapagliflozin or other Sodium/glucose cotransporter 2 (SGLT2) inhibitors (e.g. anaphylaxis, angioedema, exfoliative skin conditions).
• Use of Metformin, Thiazolidinediones, glucagon-like peptide-1 (GLP-1) receptor agonists, DPP-4 inhibitors, SGLT2 inhibitors
• Eating disorders (anorexia, bulimia) or gastrointestinal disorders.
• 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: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dapagliflozin; Patients will receive Dapagliflozin 10 mg once daily orally for 12 weeks (Forxiga® AstraZeneca company)	Drug: Dapagliflozin; oral Dapagliflozin
Active Comparator: Metformin; Patients will receive Metformin 1000 mg once daily orally for 12 weeks (control group) (Glucophage® Merck company)	Drug: Metformin; oral metformin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transvaginal ultrasonography	disappearance of PCOS	3-6 months
Fertility parameters- Luteinizing hormone	Luteinizing hormone (LH) in IU/L	3-6 months
Fertility parameters-Follicle-stimulating hormone	Follicle-stimulating hormone (FSH) in mIU/mL	3-6 months
Fertility parameters-Free androgen index	Free androgen index [ Time Frame: 3-6 months]	3-6 months
Fertility parameters-Total testosterone	Total testosterone in ng/dL	3-6 months
Menstrual diaries	Menstruation pattern	3-6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolic parameters	Fasting blood glucose (FBG) in mg/dL	3-6 months

Collaborators and Investigators

• Sponsor: Future University in Egypt
• Collaborators: October 6 University

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2024
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: August 23, 2024
• First Submitted That Met QC Criteria: August 26, 2024
• First Posted (Actual): August 28, 2024

Study Record Updates

• Last Update Posted (Actual): October 22, 2024
• Last Update Submitted That Met QC Criteria: October 18, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Pathologic Processes; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease; Genital Diseases, Female; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Ovarian Cysts; Cysts; Syndrome; Polycystic Ovary Syndrome; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Metformin; Dapagliflozin
• Other Study ID Numbers: PRC-Ph-2307003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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