Comparative Study Between (SGLT-2i) and (DPP-4i) in the Prevention of DIC (SGLT2i/DPPi)

A Comparative Clinical Study Evaluating the Efficacy of (SGLT2)Inhibitors Versus (DPP-4) Inhibitors in the Prevention of Doxorubicin-Induced Cardiotoxicity Among Egyptian Women With Breast Cancer

Background:

Breast cancer is the most frequently diagnosed malignancy among women worldwide and a major cause of morbidity and mortality. Anthracycline-based chemotherapy, particularly doxorubicin, remains a cornerstone of treatment; however, its clinical utility is limited by dose-dependent cardiotoxicity that can lead to irreversible cardiac dysfunction and heart failure. The search for effective cardioprotective interventions is therefore a key priority in cardio-oncology.

Aim:

This study aims to compare the efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors in preventing doxorubicin-induced cardiotoxicity in Egyptian women with breast cancer.

Methods:

A prospective, randomized, controlled clinical trial will be conducted at Oncology Hospital of Tanta University. Eligible adult female patients with histologically confirmed breast cancer scheduled to receive anthracycline-containing chemotherapy will be randomized into three groups: (1) control (standard care), (2) SGLT2 inhibitor group (dapagliflozin 10-25 mg daily), and (3) DPP-4 inhibitor group (sitagliptin 50-100 mg daily). Treatment will start five days before the first chemotherapy cycle and continue for six months, with follow-up for an additional six months. Cardiac function will be assessed by echocardiography (LVEF and GLS) and biomarkers (Cardiac Troponin T, and NT-proBNP). The primary endpoint is the incidence of cardiotoxicity defined by a ≥10% decline in LVEF to <50% or a >15% relative decline in GLS accompanied by biomarker elevation.

Expected Outcomes:

It is anticipated that both SGLT2 and DPP-4 inhibitors will reduce the incidence and severity of doxorubicin-induced cardiotoxicity, with SGLT2 inhibitors expected to demonstrate superior cardioprotective efficacy. Findings from this study may support the integration of cardioprotective antidiabetic agents into oncology care pathways to improve the cardiac outcomes and overall survival of breast cancer patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Other: Standard Care (in control arm); Drug: Dapagliflozin (5-10 mg daily) - SGLT2 Inhibitor Therapy; Drug: Sitagliptin (DPP4 inhibitor)

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Mai Aboelyazed Elgebaly, Associate Lecturer; Phone Number: 020 +0201061412257; Email: dr.mai.elgebaly@gmail.com
• Study Contact Backup: Name: Mai Aboelyazed Elgebaly, Associate Lecturer; Phone Number: 020 +201115064114; Email: mai.elgebaly@deltauniv.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Female, ≥18 years, Egyptian nationality.
2. Breast cancer (any stage) with planned anthracycline containing chemotherapy (intended cumulative DOX ≥240 mg/m² or epirubicin ≥360 mg/m² equivalents).
3. Baseline echo suitable for LVEF ≥53%.
4. Able to consent and comply with follow up.

Exclusion Criteria:

• • Type 1 and type 2 diabetes; history of diabetic ketoacidosis; pregnancy/lactation.

  • Symptomatic HF, cardiomyopathy, significant valvular disease, prior anthracycline exposure.
  • Baseline hypotension (SBP <95 mmHg), recurrent UTIs/mycotic infections, active foot ulcer/critical limb ischemia.
  • Inflammatory diseases, liver and kidney diseases.
  • Autoimmune diseases.
  • Other type of malignancies or metastatic diseases.
  • Patients who exposed to surgery less than one month.
  • Concomitant dexrazoxane planned upfront (allowed only for rescue; documented).
  • Known hypersensitivity to study drugs.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Arm A (Control); Usual care without prophylactic cardioprotective agent (guideline directed initiation permitted if clinically indicated post randomization; recorded and adjusted for).	Other: Standard Care (in control arm); Usual care without prophylactic cardioprotective agent (guideline directed initiation permitted if clinically indicated post randomization; recorded and adjusted for).
Active Comparator: Arm B (SGLT2i); Dapagliflozin 10 mg orally once daily (dose may increase to 25 mg if tolerated after Cycle 1) starting ≥5 days before first DOX dose and continued for 3 months.	Drug: Dapagliflozin (5-10 mg daily) - SGLT2 Inhibitor Therapy; Dapagliflozin 10 mg orally once daily (dose may increase to 25 mg if tolerated after Cycle 1) starting ≥5 days before first DOX dose and continued for 3 months.
Active Comparator: Arm C (DPP 4i); Sitagliptin 100 mg orally once daily (50 mg if eGFR 30-45 mL/min/1.73m²) starting ≥5 days before first DOX dose and continued for 3 months.	Drug: Sitagliptin (DPP4 inhibitor); Sitagliptin 100 mg orally once daily (50 mg if eGFR 30-45 mL/min/1.73m²) starting ≥5 days before first DOX dose and continued for 3 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants experiencing cardiotoxicity	Cardiotoxicity will be defined as the occurrence of any of the following during the study period: A decline in left ventricular ejection fraction (LVEF) ≥ 10% from baseline resulting in an LVEF < 50%, as measured by echocardiography, or A relative reduction in global longitudinal strain (GLS) > 15% from baseline, as assessed by speckle-tracking echocardiography. Unit of Measure: Percentage of participants experiencing cardiotoxicity (%)	Within 3 months from initiation of therapy.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change in Left Ventricular Ejection Fraction (LVEF)	Description: Absolute change in left ventricular ejection fraction from baseline to 3 months, measured by transthoracic echocardiography. Unit of Measure: Percentage points (%)	3 months
Percentage Change in Global Longitudinal Strain (GLS)	Description: Relative percentage change in global longitudinal strain from baseline to 3 months, assessed using speckle-tracking echocardiography. Unit of Measure: Percentage (%)	6 months
Time to cardiotoxicity and HF hospitalization through 6 months.		6 months
Change in serum cardiac biomarker levels e.g., troponin	Change in Cardiac Biomarkers (if applicable) Description: Change in serum cardiac biomarker levels (e.g., troponin) from baseline to 3 months. Troponin: ng/L	3 months
Change in serum cardiac biomarker levels (e.g., NT-proBNP)	Description: Change in serum cardiac biomarker levels (e.g., NT-proBNP) from baseline to 3 months. NT-proBNP: pg/mL	3 months
All cause mortality and cancer therapy interruptions due to cardiac reasons.		6 months

Collaborators and Investigators

• Sponsor: Tanta University
• Investigators: Principal Investigator: Mohamed Abdelhamid Almeldein, Professor, Tanta University; Principal Investigator: Mohamed Elhussieny Shams, Professor, Mansoura University; Study Director: Haidy Mahmoud Sami, Lecturer, Delta University; Study Director: Osama Hamid Shoaeb, Associate Professor, Tanta University

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: November 21, 2025
• First Submitted That Met QC Criteria: February 25, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 25, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Protease Inhibitors; Enzyme Inhibitors; Health Services Administration; Health Care Quality, Access, and Evaluation; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Pharmacologic Actions; Chemical Actions and Uses; Quality of Health Care; Quality Indicators, Health Care; Pyrazines; Triazoles; Sitagliptin Phosphate; Dipeptidyl-Peptidase IV Inhibitors; Standard of Care; dapagliflozin
• Other Study ID Numbers: 2467Q8

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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