Liraglutide Protects Lungs from Sepsis Damage by Restoring Surfactant Production | Research

The takeaway

The GLP-1 drug liraglutide protected mice from sepsis-induced lung injury by restoring pulmonary surfactant and inhibiting excessive autophagy.

Liraglutide prolonged survival in sepsis-induced ALI
Mice treated with liraglutide after sepsis-induced acute lung injury survived longer, with restored surfactant protein expression and reduced lung inflammation — effects blocked by the autophagy activator rapamycin.

What the researchers found

Liraglutide, a GLP-1 receptor agonist, protected mice from sepsis-induced acute lung injury (ALI) by restoring pulmonary surfactant production and inhibiting excessive autophagy. Treated mice survived longer, had less lung inflammation, less pulmonary edema (lower wet/dry weight ratio), and less cell death compared to untreated ALI mice. In cell culture, liraglutide reversed the damage caused by bacterial toxins (LPS) and restored expression of surfactant proteins SP-A and SP-B. The protective effects were blocked by rapamycin (an autophagy activator), confirming that liraglutide works by inhibiting autophagy.

Why it matters

Sepsis-induced acute lung injury is a life-threatening condition with limited treatment options and high mortality. This study reveals an unexpected therapeutic role for liraglutide — a drug millions take for diabetes and obesity — in protecting lungs during sepsis. The mechanism through pulmonary surfactant regulation is particularly interesting because surfactant dysfunction is a hallmark of acute respiratory distress syndrome (ARDS).

How the study worked

C57BL/6 mice were given an ALI model and then treated with subcutaneous liraglutide at different concentrations. Researchers measured survival rates, lung wet/dry weight ratios, inflammatory markers in bronchoalveolar lavage fluid, lung tissue damage, and cell death. In parallel, MLE-12 lung epithelial cells were stimulated with LPS and treated with liraglutide, measuring cell viability, proliferation, apoptosis, surfactant protein expression (SP-A, SP-B), and autophagy markers. Rapamycin was used to confirm the autophagy-dependent mechanism.

Who was studied

C57BL/6 male mice with sepsis-induced acute lung injury; MLE-12 mouse lung epithelial cells

What this study cannot tell us

This is an animal study in mice with a chemically induced sepsis model, which may differ from the complexity of human sepsis. The cell line used (MLE-12) is a mouse lung epithelial cell line, not primary human cells. The study did not test different timing windows for liraglutide administration, and the optimal dose for lung protection in humans is unknown. The sepsis model may not capture all aspects of clinical ALI/ARDS.

How to read the evidence

This is a preliminary animal study combining in vivo mouse experiments with in vitro cell culture work. While the mechanism is well-demonstrated through rapamycin reversal, all findings are preclinical and require human validation before clinical application.

When this study was published

Published in 2024, this is a recent study contributing to the active research area of GLP-1 drug repurposing for inflammatory and critical care conditions.

The bigger picture

This study adds to a growing body of research showing GLP-1 drugs have anti-inflammatory and organ-protective effects far beyond blood sugar and weight management. The lung protection findings are part of an emerging pattern: GLP-1 receptor agonists appear to reduce inflammation and tissue damage across multiple organ systems. If these effects translate to humans, existing GLP-1 drugs could be repurposed for critical care settings.

Questions still open

Could liraglutide or other GLP-1 drugs be used in ICU patients with ARDS to improve lung function?
Do patients already taking GLP-1 drugs for diabetes have better outcomes if they develop sepsis?
Is the lung-protective dose of liraglutide similar to or different from the doses used for diabetes and obesity?

Common questions

How does liraglutide protect the lungs during sepsis?

During sepsis, excessive autophagy (a cellular self-destruction process) damages lung cells that produce surfactant — the coating that keeps air sacs open. Liraglutide blocks this excessive autophagy, allowing lung cells to survive and continue making surfactant proteins SP-A and SP-B, which reduces lung inflammation, fluid buildup, and respiratory failure.

Could people taking Ozempic or Saxenda be protected if they get sepsis?

This study was done in mice, so we can't yet say whether people on GLP-1 drugs would have better outcomes during sepsis. However, the findings suggest this is worth investigating. Epidemiological studies looking at sepsis outcomes in GLP-1 drug users, and clinical trials in ICU patients, would be needed to answer this question.

Read the original research

Liraglutide alleviates sepsis-induced acute lung injury by regulating pulmonary surfactant through inhibiting autophagy.

Immunopharmacology and immunotoxicology, 46(5), 573-582

View on PubMed ↗Publisher’s paper ↗

Citation

Guo, Junping; Zhang, Xiao; Pan, Ran; Zheng, Yueliang; Chen, Wei; Wang, Lijun. (2024). Liraglutide alleviates sepsis-induced acute lung injury by regulating pulmonary surfactant through inhibiting autophagy.. Immunopharmacology and immunotoxicology, 46(5), 573-582. https://doi.org/10.1080/08923973.2024.2384897