Cardioprotective Effect of Empagliflozin in Breast Cancer Patients

September 7, 2026 updated by: Mai Abo Elyazeed Hassan Hamouda, Tanta University

Effects of Empagliflozin Versus Metformin in Women With Breast Cancer Receiving Doxorubicin-Based Chemotherapy: A Prospective Randomized Controlled Cardio-Oncology Trial

Background: Doxorubicin (DOX) remains a cornerstone in adjuvant and neoadjuvant therapy for breast cancer, but its utility is hindered by dose-dependent cardiotoxicity. Both SGLT2 inhibitors (Empagliflozin) and Biguanides (Metformin) have demonstrated off-target cardioprotective and metabolic properties in preclinical and clinical settings.

Objective: To compare the cardioprotective efficacy, safety, and metabolic/oncologic outcomes of Empagliflozin versus Metformin in non-diabetic or controlled-diabetic women with breast cancer undergoing doxorubicin-based chemotherapy.

Design: Prospective, 3-arm, open-label (or double-blind), randomized controlled clinical trial (RCT).

Duration: 18 months

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Background & Rationale Anthracyclines, primarily Doxorubicin, induce cardiotoxicity through reactive oxygen species (ROS) accumulation, topoisomerase II-beta inhibition, mitochondrial dysfunction, and cardiomyocyte apoptosis.

  • Empagliflozin (SGLT2 inhibitor): Reduces oxidative stress, attenuates cardiac inflammation, improves myocardial energy bioenergetics, and prevents adverse left ventricular remodeling independently of glycemic status.
  • Metformin (AMPK activator): Restores autophagic flux, preserves mitochondrial membrane potential, reduces ROS production, and exhibits anti-tumor proliferation effects.

  • Gaps in Knowledge: While both drugs individually show promise against anthracycline-induced cardiotoxicity (AIC), direct head-to-head clinical trials comparing an SGLT2i versus Metformin during active anthracycline treatment are lacking.

    3. Study Hypothesis

  • Primary Hypothesis: Prophylactic administration of Empagliflozin or Metformin significantly attenuates the subclinical decline in Left Ventricular Ejection Fraction (LVEF) and Global Longitudinal Strain (GLS) compared to standard care in women receiving doxorubicin.

  • Secondary Hypothesis: Empagliflozin demonstrates superior reduction in cardiac biomarker elevation (hs-cTnI, NT-proBNP) and microvascular strain compared to Metformin.

    4. Study Objectives Primary Objective To compare the changes in left ventricular systolic function (measured via baseline to 6-month Echocardiographic GLS and LVEF) among the Empagliflozin group, Metformin group, and Control group.

Secondary Objectives

  1. Evaluate subclinical myocardial injury via serum biomarkers: High-sensitivity Cardiac Troponin I (hs-cTnI) and N-terminal pro-B-type Natriuretic Peptide (NT-proBNP).
  2. Monitor metabolic profiles (fasting blood glucose, HbA1c, and lipid profile).
  3. Evaluate patient-reported outcomes (Karnofsky Performance Scale / Minnesota Living with Heart Failure Questionnaire).
  4. Compare the safety profile, chemotherapy completion rates, and short-term oncologic response (pathological Complete Response in neoadjuvant settings).

  5. Methodology & Study Design 5.1 Study Settings and Design

    • Design: Prospective, randomized, parallel-group, active-controlled trial.
    • Setting: Tanta Oncology Hospital / Cardio-Oncology Center. 5.2 Participant Eligibility Criteria

Inclusion Criteria:

  1. Adult females (≥18 years) with histologically confirmed breast cancer.
  2. Scheduled to receive doxorubicin-based chemotherapy regimens (e.g., AC regimen: Doxorubicin + Cyclophosphamide every 2 or 3 weeks for 4 cycles).
  3. Baseline LVEF ≥ 55 on transthoracic echocardiography with normal baseline GLS.
  4. Estimated Glomerular Filtration Rate (eGFR) < 45 mL/min/1.73 m2
  5. Written informed consent provided.

Exclusion Criteria:

  1. Prior exposure to anthracyclines, mediastinal radiation, or anti-HER2 therapy.
  2. Pre-existing heart failure, coronary artery disease, or LVEF $< 55\%$.
  3. Uncontrolled Type 2 Diabetes Mellitus (HbA1c $> 8.5\%$) or Type 1 Diabetes Mellitus.
  4. Severe renal impairmet (eGFR < 45 mL/min/1.73 m2) or hepatic dysfunction.
  5. History of recurrent Urinary Tract Infections (UTIs), genital mycotic infections, or ketoacidosis (for Empagliflozin safety).
  6. Hypersensitivity to Empagliflozin or Metformin.

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Egypt
    • Elgharbeya
      • Tanta, Elgharbeya, Egypt, GHR
        • Tanta University
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Mohamed Abdelhamid Alameldein, Professor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Adult females (≥18 years) with histologically confirmed breast cancer.
  2. Scheduled to receive doxorubicin-based chemotherapy regimens (e.g., AC regimen: Doxorubicin + Cyclophosphamide every 2 or 3 weeks for 4 cycles).
  3. Baseline LVEF ≥ 55 on transthoracic echocardiography with normal baseline GLS.
  4. Estimated Glomerular Filtration Rate (eGFR) < 45 mL/min/1.73 m2
  5. Written informed consent provided

Exclusion Criteria:

  1. Prior exposure to anthracyclines, mediastinal radiation, or anti-HER2 therapy.
  2. Pre-existing heart failure, coronary artery disease, or LVEF $< 55\%$.
  3. Uncontrolled Type 2 Diabetes Mellitus (HbA1c $> 8.5\%$) or Type 1 Diabetes Mellitus.
  4. Severe renal impairmet (eGFR < 45 mL/min/1.73 m2) or hepatic dysfunction.
  5. History of recurrent Urinary Tract Infections (UTIs), genital mycotic infections, or ketoacidosis (for Empagliflozin safety).
  6. Hypersensitivity to Empagliflozin or Metformin.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Arm A (Control)
Standard oncologic care without cardioprotective intervention followed concurrently for 12 weeks
Active Comparator: Arm B (Empaglflozin)
Empagliflozin 10 mg orally once daily initiated 1 week prior to chemotherapy; continued for 12 weeks
Drug: Empagliflozin (EMPA)
Intervention group: A group in which patients receive Empagliflozin drug at a dose of 10 mg once in the day, or along with chemotherapy.
Active Comparator: Arm C (Metformin)
Metformin 500 mg orally twice daily (escalated to 1000 mg twice daily as tolerated) initiated 1 week prior to chemotherapy; continued for 12 weeks
Drug: Metformin
Metformin 500 mg orally twice daily (escalated to 1000 mg twice daily as tolerated) Initiated 1 week prior to chemotherapy; continued for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
LVEF (Left ventricular ejection fraction) : The left ventricular drain fraction or the amount of blood pumped from the left ventricle with each contraction.
Time Frame: 6 months
LVEF from baseline (T0) to 6-month follow-up (T3), measured by 2D Speckle-Tracking Echocardiography.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tanta University

Investigators

  • Study Director: Mohamed Abdelhamid Almeldein, Professor, Tanta University
  • Study Director: Mohamed Abdelhamid Alameldein, Professor, Tanta University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2026

Primary Completion (Estimated)

September 30, 2028

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

September 7, 2026

First Submitted That Met QC Criteria

September 7, 2026

First Posted (Actual)

September 11, 2026

Study Record Updates

Last Update Posted (Actual)

September 11, 2026

Last Update Submitted That Met QC Criteria

September 7, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DeltaU

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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