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NCT Number: NCT07436663

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

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.

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Key information

Sex eligibility

Female

Study type

Interventional

Phase

Phase 4

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

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.

Treatment and study plan

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.

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.

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).

Primary outcomes

  1. Percentage of participants experiencing cardiotoxicity

    Time frame: Within 3 months from initiation of therapy.

    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 (%)

Secondary outcomes

  1. Percentage Change in Left Ventricular Ejection Fraction (LVEF)

    Time frame: 3 months

    Description:

    Absolute change in left ventricular ejection fraction from baseline to 3 months, measured by transthoracic echocardiography.

    Unit of Measure: Percentage points (%)

  2. Percentage Change in Global Longitudinal Strain (GLS)

    Time frame: 6 months

    Description:

    Relative percentage change in global longitudinal strain from baseline to 3 months, assessed using speckle-tracking echocardiography.

    Unit of Measure: Percentage (%)

  3. Time to cardiotoxicity and HF hospitalization through 6 months.

    Time frame: 6 months

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

    Time frame: 3 months

    Change in Cardiac Biomarkers (if applicable)

    Description:

    Change in serum cardiac biomarker levels (e.g., troponin) from baseline to 3 months.

    Troponin: ng/L

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

    Time frame: 3 months

    Description:

    Change in serum cardiac biomarker levels (e.g., NT-proBNP) from baseline to 3 months.

    NT-proBNP: pg/mL

  6. All cause mortality and cancer therapy interruptions due to cardiac reasons.

    Time frame: 6 months

Study contacts

Contact information is provided by the study sponsor or research team.

Mai Aboelyazed Elgebaly, Associate Lecturer

CONTACT

[email protected]

+0201061412257 ext. 020

Mai Aboelyazed Elgebaly, Associate Lecturer

CONTACT

[email protected]

+201115064114 ext. 020

Sponsors and collaborators

Lead sponsor

Tanta University

Other

Registry information

Official study title

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

Acronym: SGLT2i/DPPi

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Feb 27, 2026
Registry last updated
Feb 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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