Sodium-Glucose Co-Transporter-2 Inhibitors as Adjuvant Therapy With Letrozole in Induction of Ovulation (SGLT-2/PCOS)

Sodium-Glucose Co-Transporter-2 Inhibitors as Adjuvant Therapy With Letrozole in Induction of Ovulation in Women With Polycystic Ovarian Syndrome

The aim of the study is to assess the efficacy of adjuvant therapy dapagliflozin, metformin as monotherapy and combination of both in comparison to control group in induction of ovulation with letrozole in women PCOS, focusing specifically on rates of ovulation and pregnancy.

Study Overview

• Status: Completed
• Conditions: Induction of Ovulation
• Intervention / Treatment: Drug: Metformin 1000 mg; Drug: Letrozole 2.5Mg Tablet; Drug: Dapagliflozin 10 mg; Drug: Combined Dapagliflozin-Metformin 5/1000mg

Detailed Description

The study will be a randomized controlled clinical trial. Once the eligibility from screening visit is determined prior to baseline visit, randomization will be made by computer randomization for women who are admitted to Beni-Suef University Hospital. The Sample size will be 500 divided equally into 4 groups calculated with power=0.8.

Before initiation of the study, the population will be divided randomly into 4 equal groups: group A, B, C and D. The adjuvant therapy of each group will be group (A) Metformin , group (B) Dapagliflozin , Group(C) Combined Dapagliflozin-Metformin and group (D) with no adjuvant therapy (control group). The adjuvant therapy will be taken once daily with a main meal and started one month before initiation of letrozole. All groups will take letrozole 2.5mg twice daily from the third day of the cycle for 5 days.

Ovulation rate (percentage of ovulatory cycles in the whole follow up period),Pregnancy rate (clinical pregnancy will be considered when an intrauterine gestational sac is seen and presence of a fetal heartbeat),Serum progesterone on day 21,Endometrial thickness at the time of ovulation and Weight, waist/hip ratio, height and body mass index (BMI) will be measured

• Study Type: Interventional
• Enrollment (Actual): 500
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Banī Suwayf, Egypt, 62517
    • Gynecology and Reproductive department in Beni-Suef University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Pre-menopausal women aged 20-40 with primary or secondary infertility and PCOS which render them unable to become pregnant. Diagnosis of PCOS will based on European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine (ESHRE/ASRM) criteria, the diagnosis is made when at least two of the following criteria are met: oilgo and/or anovulation (infrequent or no ovulation), clinical and/or biochemical signs of hyperandrogenism including hirsutism, acne and/or increased testosterone levels or polycystic ovaries on ultrasound (defined as those containing at least 12 follicles measuring 2-9 mm in diameter arranged peripherally around an echo-dense stroma and/or with increased ovarian volume of at least 10 ml).

Exclusion Criteria:

Other causes of hyperandrogenism mimic PCOS such as congenital adrenal hyperplasia, Cushing's syndrome, or androgen secreting tumors are excluded.

Persistent hyperprolactinemia, thyroid dysfunction defined as TSH < 0.2 mIU/ML or >5.5 mIU/mL) or patients with menopausal levels of FSH (> 15 mIU/mL) (A normal level within the last year is adequate for enter the study).

Liver disease is defined as AST or ALT > 2 times normal or total bilirubin >2.5 mg/dL, kidney disease defined as BUN > 30 mg/dL or serum creatinine> 1.4 mg/dL or significant anemia defined as Hemoglobin < 10 mg/dL.

Women with Type I or II diabetes mellitus who are poorly controlled (defined as a HA1c level > 7.0%).

Untreated poorly controlled hypertension is defined as a systolic blood pressure ≥ 160 mm Hg or a diastolic ≥ 100 mm Hg obtained on two measures obtained at least 60 minutes apart.

History of deep venous thrombosis, pulmonary embolus, or cerebrovascular accident.

Women who have undergone a bariatric surgery procedure in the recent past (<12 months) and are in a period of acute weight loss or have been advised against pregnancy by their bariatric surgeon.

Presence of any urinary symptom such as frequency, urgency, or bloody micturition.

In case of metabolic acidosis, osteoporosis, endometrial hyperplasia, or endometrial neoplasia.

Women who had gonadotropin induction, ovarian drilling before or women with hypergonadotropic hypogonadism or functional ovarian cysts (> 5cm).

Criteria of IVF/ICSI as poor Response, no Eggs or ectopic pregnancy. Women who receive antidiabetic medications such as insulin, thiazolidinediones, acarbose, or sulfonylureas are likely to confound the effects of study medication or who are currently receiving metformin XR for a diagnosis of Type I or Type II diabetes or for PCOS are also specifically excluded.

Concomitant use of medication that could interfere with the absorption, metabolism, and excretion of drugs involved in the study as the use of Furosemide, cimetidine increase metformin concentration and nifedipine enhances the absorption of metformin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: "metformin"; will take Metformin 1000mg as adjuvant therapy	Drug: Metformin 1000 mg; will take Metformin 1000 mg once daily with a main meal and started one month before initiation of the first cycle of induction.; Drug: Letrozole 2.5Mg Tablet; will take letrozole 2.5mg twice daily from the third day of the cycle for 5 days.
Experimental: "Dapagliflozin"; will take Dapagliflozin 10mg as adjuvant therapy	Drug: Letrozole 2.5Mg Tablet; will take letrozole 2.5mg twice daily from the third day of the cycle for 5 days.; Drug: Dapagliflozin 10 mg; will take Dapagliflozin 10mg once daily with a main meal and started one month before initiation of the first cycle of induction.
Experimental: "Dapagliflozin-Metformin"; will take combined Dapagliflozin-Metformin 5/1000 as adjuvant therapy	Drug: Letrozole 2.5Mg Tablet; will take letrozole 2.5mg twice daily from the third day of the cycle for 5 days.; Drug: Combined Dapagliflozin-Metformin 5/1000mg; will take Combined Dapagliflozin-Metformin 5/1000mg once daily with a main meal and started one month before initiation of the first cycle of induction.
Other: "control"; will take letrozole 2.5mg the no adjuvant therapy	Drug: Letrozole 2.5Mg Tablet; will take letrozole 2.5mg twice daily from the third day of the cycle for 5 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ovulation rate	percentage of ovulatory cycles	"through study completion, an average of 1 year".
Pregnancy rate	when an intrauterine gestational sac is seen and presence of a fetal heartbeat)	"through study completion, an average of 1 year".

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum progesterone	Serum progesterone	"through study completion, an average of 1 year".
Endometrial thickness	Endometrial thickness	"through study completion, an average of 1 year".
Weight	Weight in kilogram	"through study completion, an average of 1 year".

Collaborators and Investigators

• Sponsor: Beni-Suef University

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2023
• Primary Completion (Actual): July 1, 2024
• Study Completion (Actual): October 30, 2025

Study Registration Dates

• First Submitted: August 8, 2025
• First Submitted That Met QC Criteria: May 9, 2026
• First Posted (Actual): May 15, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 9, 2026
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pharmaceutical Preparations; Dosage Forms; Azoles; Nitriles; Biguanides; Guanidines; Amidines; Triazoles; Letrozole; Metformin; Tablets; dapagliflozin
• Other Study ID Numbers: IORG2226240

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes