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

NCT07436663 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: 2467Q8
• Study Type: interventional
• Target: 150
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Percentage Change in Left Ventricular Ejection Fraction (LVEF)

  3 months

• Percentage Change in Global Longitudinal Strain (GLS)

  6 months

• Time to cardiotoxicity and HF hospitalization through 6 months.

  6 months

• Change in serum cardiac biomarker levels e.g., troponin

  3 months

• Change in serum cardiac biomarker levels (e.g., NT-proBNP)

  3 months

Study Arms (3)

Arm A (Control)

PLACEBO COMPARATOR

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)

Arm B (SGLT2i)

ACTIVE COMPARATOR

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

Arm C (DPP 4i)

ACTIVE COMPARATOR

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)

Interventions

Dapagliflozin (5-10 mg daily) - SGLT2 Inhibitor Therapy DRUG

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.

Arm B (SGLT2i)

Sitagliptin (DPP4 inhibitor) DRUG

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.

Arm C (DPP 4i)

Standard Care (in control arm) OTHER

Usual care without prophylactic cardioprotective agent (guideline directed initiation permitted if clinically indicated post randomization; recorded and adjusted for).

Arm A (Control)

Eligibility Criteria

• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tanta University: lead

MeSH Terms

Conditions

Breast Neoplasms

Interventions

dapagliflozin; Sitagliptin Phosphate; Dipeptidyl-Peptidase IV Inhibitors; Standard of Care

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Mohamed Abdelhamid Almeldein, Professor

  Tanta University

  PRINCIPAL INVESTIGATOR

• Mohamed Elhussieny Shams, Professor

  Mansoura University

  PRINCIPAL INVESTIGATOR

• Haidy Mahmoud Sami, Lecturer

  Delta University

  STUDY DIRECTOR

• Osama Hamid Shoaeb, Associate Professor

  Tanta University

  STUDY DIRECTOR

Central Study Contacts

Mai Aboelyazed Elgebaly, Associate Lecturer

CONTACT

+0201061412257; dr.mai.elgebaly@gmail.com

Mai Aboelyazed Elgebaly, Associate Lecturer

CONTACT

+201115064114; mai.elgebaly@deltauniv.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Lecturer

Model Details: Interventional, prospective, randomized, parallel controlled clinical trial

Study Record Dates

• First Submitted: November 21, 2025
• First Posted: February 27, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 27, 2026

Record last verified: 2026-02