Cardioprotective Effect of Empagliflozin in Breast Cancer Patients

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

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.