Empagliflozin vs Metformin in PCOS

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.

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.

Study Overview

• Status: Completed
• Conditions: Polycystic Ovary Syndrome
• Intervention / Treatment: Drug: Empagliflozin; Drug: Metformin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • East Yorkshire
    • Hull, East Yorkshire, United Kingdom, HU3 2RW
      • Michael White Centre for Diabetes and Endocrinology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Women, aged 18-45 years (inclusive), with confirmed diagnosis of PCOS based on Rotterdam criteria.
2. Presence of both irregular periods and biochemical hyperandrogenaemia
3. Body mass index ≥25
4. Negative pregnancy test during screening visit and agree to use barrier contraception during the study period.

Exclusion Criteria:

1. Non-classical 21-hydroxylase deficiency, hyperprolactinaemia, Cushing's disease and androgen-secreting tumours will be excluded by appropriate tests.
2. Confirmed diagnosis of diabetes or pre-diabetes.
3. Ongoing, inadequately controlled thyroid disorder (subjects on thyroid hormone replacement therapy must be on stable dose for at least 3 months before screening day)
4. History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and in-situ carcinoma).
5. History or plan of any form of gastrointestinal tract surgery.
6. History of pancreatitis (Acute or Chronic).
7. Any disorder which in the opinion of the investigator might jeopardize subject's safety.

8. 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
9. Female who is pregnant, breast feeding or intended to become pregnant or of child bearing potential not using adequate contraceptive methods.
10. eGFR<60
11. Hypersensitivity to lactose
12. Severe hepatic impairment (ALT >3 times ULN)
13. Women with history of recurrent urinary tract infections.
14. Haematocrit above the upper limit of normal range.
15. Have been involved in another medicinal trial (CTIMP) within the past four weeks.
16. Known hypersensitivity to the Investigational Medicinal Products or any of their excipients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hull University Teaching Hospitals NHS Trust
• Investigators: Principal Investigator: Thozhukat Sathyapalan, MBBS FRCP MD, University of Hull/Hull and East Yorkshire Hospitals NHS Trust

Publications and helpful links

General Publications

• Javed Z, Papageorgiou M, Deshmukh H, Rigby AS, Qamar U, Abbas J, Khan AY, Kilpatrick ES, Atkin SL, Sathyapalan T. Effects of empagliflozin on metabolic parameters in polycystic ovary syndrome: A randomized controlled study. Clin Endocrinol (Oxf). 2019 Jun;90(6):805-813. doi: 10.1111/cen.13968. Epub 2019 Apr 2.

Helpful Links

• Publication Link

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2017
• Primary Completion (Actual): April 2, 2018
• Study Completion (Actual): April 2, 2018

Study Registration Dates

• First Submitted: December 28, 2016
• First Submitted That Met QC Criteria: December 28, 2016
• First Posted (Estimate): January 2, 2017

Study Record Updates

• Last Update Posted (Actual): July 15, 2019
• Last Update Submitted That Met QC Criteria: July 11, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• 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; Sodium-Glucose Transporter 2 Inhibitors; Metformin; Empagliflozin
• Other Study ID Numbers: Version 3.0

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