Empagliflozin and intermittent fasting as a strategy to mitigate anthracycline-induced cardiotoxicity

Q: What is the clinical evidence from this study?

Population: Anthracycline-induced cardiotoxicity (n=26). Intervention: Empagliflozin and Time-Restricted Feeding (TRF) vs. Doxorubicin alone. Primary outcome: Cardiovascular damage and remodeling.

Juliano Moreira Reis Filho; Ivan Lobo de Sousa Marques; Lucas M. Kangussu; Alexandre Dantas Costa; Gabrielly Carvalho de Mattos; Flávio A. Amaral; Artur Santos-Miranda; Julliane V. Joviano‐Santos

doi:10.1038/s41598-026-35790-1

March 3, 2026Scientific ReportsOpen Access

Empagliflozin and intermittent fasting as a strategy to mitigate anthracycline-induced cardiotoxicity

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Key result

Empagliflozin and time-restricted feeding individually mitigate doxorubicin-induced CV damage in rats and one clinical case.

n=26

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Why the study?

Given anthracycline-induced cardiotoxicity, integrating pharmacological and nonpharmacological interventions like empagliflozin and intermittent fasting is of growing interest in cardio-oncology.

Does empagliflozin and/or time-restricted feeding mitigate doxorubicin-induced cardiotoxicity in an experimental rat model and a clinical case?

Key Points

To assess whether empagliflozin, alone or combined with time-restricted feeding, mitigates doxorubicin-induced cardiovascular toxicity in an experimental rat model and a clinical case.
Rats were assigned to control, Dox (12 mg/kg), Dox + EMPA (10 mg/kg), Dox + TRF (16 h/8 h fasting), or Dox + EMPA + TRF groups for 4 weeks.
A 56-year-old female breast cancer patient receiving doxorubicin (total dose 240 mg/m2 across 4 cycles) was treated with EMPA (10 mg/day) and TRF for 3 months.
Hemodynamic parameters, electrocardiograms, histology, hematology, and inflammatory cytokine expression (TNF, IL-1β, IL-10, TGF-β) were evaluated in animals, alongside clinical monitoring in the patient.
In rats, Dox increased systolic pressure (165 ± 13.9 mmHg vs. 114.8 ± 7.5 mmHg in controls) and diastolic pressure (127 ± 13.4 mmHg vs. 89.6 ± 8.8 mmHg), both of which were significantly attenuated by EMPA or TRF individually, though combined treatment showed no significant difference compared to Dox alone.
QTc prolongation was significantly reduced by EMPA, TRF, or their combination, while EMPA alone reversed Dox-induced P wave and QRS complex alterations.
EMPA reduced cardiac TNF expression by ~80% and TRF by ~65%, whereas TRF alone suppressed IL-1β by nearly 70% and combination therapy markedly increased IL-10 and TGF-β expression.

Structured PICO

Does empagliflozin and/or time-restricted feeding mitigate doxorubicin-induced cardiotoxicity in an experimental rat model and a clinical case?

P

Population

Female Wistar rats (n=25, 5 per group) and one 56-year-old female clinical case with invasive breast carcinoma (estrogen receptor-positive, HER2-negative) undergoing doxorubicin therapy.

I

Intervention

Empagliflozin (10 mg/kg daily orally in rats; 10 mg/day in patient) and/or Time-Restricted Feeding (16 h fasting/8 h feeding) for 4 weeks in the animal model and 3 months in the clinical case.

C

Comparator

In the animal model: Control group (no doxorubicin) and Doxorubicin-only group (12 mg/kg weekly intraperitoneally).

O

Outcome

Cardiovascular parameters including hemodynamic (systolic, diastolic, and mean arterial pressures), electrocardiographic (P wave, QRS, QTc), and histological (myocardial remodeling and inflammation) changes.surrogate

Empagliflozin and time-restricted feeding individually mitigated doxorubicin-induced hemodynamic, electrocardiographic, and histological cardiotoxicity in a rat model, though their combination did not show additive benefits.

Limitations

Initial clinical analysis was conducted on a single case
Further clinical studies are needed to confirm safety and efficacy in humans
The benefits of each treatment may depend on the degree of cardiac impairment, the metabolic state of the heart, and the duration of Dox exposure, which were not explored in this study
Further clinical studies are needed to confirm their safety

Implication

Should not yet alter cardio-oncology practice; extends evidence for empagliflozin in doxorubicin cardiotoxicity.

Abstract

Empagliflozin (EMPA) has shown cardioprotective potential by enhancing myocardial energy availability, a mechanism also observed with intermittent fasting strategies, such as time-restricted feeding (TRF). Given the cardiotoxicity of anthracyclines as Doxorubicin (Dox), integrating pharmacological and nonpharmacological interventions is of growing interest in cardio-oncology. This study assessed EMPA, alone or with TRF, in mitigating Dox-induced cardiovascular damage using both an experimental model and a clinical case. Rats were assigned to control, Dox, Dox + EMPA, Dox + TRF, or Dox + EMPA + TRF groups. Treatments included Dox (12 mg/kg), EMPA (10 mg/kg), and TRF (16 h/8 h), for four weeks. In the clinical case, a cancer patient undergoing Dox therapy received EMPA (10 mg/day) followed by TRF for three months. Cardiovascular parameters were measured. In animals, Dox significantly increased systolic, diastolic, and mean arterial pressures, mitigated by EMPA or TRF individually, with no additive effect when combined. EMPA partially normalized Dox-induced P wave and QRS alterations, while EMPA, TRF, or both reduced QTc prolongation. Histology showed Dox-induced myocardial remodeling and inflammation, which were attenuated by all treatments, restoring cardiomyocyte occupancy, reducing extracellular matrix expansion, and decreasing inflammatory infiltrate. All co-treatments prevented Dox-related leukopenia, normalizing leukocyte counts. Mechanistically, EMPA and TRF modulated Dox-induced inflammation in distinct ways: both (alone or combined) lowered TNF, TRF alone produced the strongest IL-1β suppression, the combined treatment increased IL-10 and TGF-β significantly. Clinically, the patient experienced weight loss, stable blood pressure, and cardiovascular stability although a rise in troponin levels. In conclusion, individual EMPA and TRF may help mitigate Dox-induced cardiotoxicity in certain contexts, though further clinical studies are needed to confirm their safety.

Discussion

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Cite This Study

Filho et al. (2026) studied Anthracycline-induced cardiotoxicity (n=26). Empagliflozin and Time-Restricted Feeding (TRF) vs. Doxorubicin alone was evaluated on Cardiovascular damage and remodeling. Empagliflozin and time-restricted feeding individually mitigated doxorubicin-induced cardiovascular damage in rats, and maintained cardiovascular stability in a single clinical case.

synapsesocial.com/papers/69a91dedd6127c7a504c14bb https://doi.org/10.1038/s41598-026-35790-1

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Empagliflozin and intermittent fasting as a strategy to mitigate anthracycline-induced cardiotoxicity

Figures

Key Points

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

Empagliflozin and intermittent fasting as a strategy to mitigate anthracycline-induced cardiotoxicity

Figures

Key Points

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

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