First Test of Liraglutide as COVID-19 Treatment: Safe and Shows Promising Immune Signals | Research

The takeaway

In the first trial of a GLP-1 drug for acute COVID-19, liraglutide was safe and well-tolerated in 13 hospitalized patients, with milder cases showing reduced inflammation markers, improved heart function, and decreased CD147 receptor levels.

First-in-disease GLP-1 trial
This is the first clinical test of a GLP-1 drug for acute COVID-19 — all 13 patients tolerated treatment and were alive at 30 days, with encouraging biomarker signals in milder cases

What the researchers found

Liraglutide (0.6 mg subcutaneously daily for 5 days) was well tolerated by all 13 hospitalized COVID-19 pneumonia patients, with 100% survival at 30 days. In the non-critical group, plasma soluble CD147 levels decreased at day 5, while critical care patients showed an increase in CD147 between days 0-5.

Non-critical patients also demonstrated improved right and left ventricular function on echocardiography, reduced plasma troponin levels (indicating less cardiac damage), increased CD147 expression on T lymphocytes (potentially enhancing immune function), and reduced plasma IL-8 (an inflammatory chemokine). These divergent patterns between mild and severe cases suggest liraglutide's benefits may be most pronounced when given early in disease, before critical illness develops.

Why it matters

COVID-19 taught the medical community the importance of having diverse treatment options ready for pandemics. This study demonstrates that GLP-1 drugs — already widely used for diabetes and obesity — could potentially be repurposed for viral infections that cause systemic inflammation and cardiac damage. The CD147 receptor downregulation is particularly interesting because it could reduce viral cell entry, adding an antiviral dimension to GLP-1 drugs' known anti-inflammatory properties.

How the study worked

This was an open-label, single-center, phase II safety and tolerability study. Thirteen patients hospitalized with COVID-19 pneumonia received liraglutide 0.6 mg subcutaneously daily for 5 days as add-on therapy to standard of care, initiated within 48 hours of hospital presentation. Biomarker responses (soluble CD147, troponin, IL-8, T lymphocyte CD147 expression) and echocardiographic parameters were measured. Outcomes were compared between patients requiring critical care admission and those who did not.

What this study cannot tell us

This was a very small (n=13), open-label study with no control group, making it impossible to attribute improvements specifically to liraglutide versus natural disease course. The low liraglutide dose (0.6 mg) was chosen for safety but may not represent the optimal therapeutic dose. The divergent responses between critical and non-critical patients may reflect disease severity rather than differential drug effects. The study was conducted during a specific COVID-19 wave and may not generalize to other variants.

How to read the evidence

This is a very small (n=13), open-label, single-center phase II safety study without a control group. While it provides important proof-of-concept safety data, it cannot demonstrate efficacy. The biomarker findings are exploratory and hypothesis-generating.

When this study was published

Published in 2025, this study addresses a specific pandemic-era question. While the acute COVID-19 treatment landscape has evolved, the findings about GLP-1 drugs' anti-inflammatory and CD147-modulating effects remain relevant for understanding these drugs' pleiotropic properties and pandemic preparedness.

The bigger picture

GLP-1 receptor agonists continue to reveal therapeutic potential far beyond diabetes. This study adds infectious disease to the growing list of conditions where GLP-1 drugs show promise, alongside cardiovascular protection, kidney disease, and neurodegeneration. The mechanism here — reducing a viral entry receptor while dampening inflammation — could be relevant to future pandemic preparedness, as CD147 is used by multiple viruses beyond SARS-CoV-2.

Questions still open

Would higher doses of liraglutide or more potent GLP-1 drugs like semaglutide produce stronger anti-inflammatory and CD147-lowering effects in COVID-19?
Could early GLP-1 drug treatment prevent progression from mild to severe COVID-19?
Is the CD147 downregulation mechanism relevant to other viral infections where CD147 serves as an entry receptor?

Common questions

Why would a diabetes drug help with COVID-19?

GLP-1 drugs like liraglutide have anti-inflammatory effects beyond blood sugar control. They also reduce a receptor called CD147, which is one of the receptors COVID-19 uses to enter human cells. By lowering CD147 and dampening inflammation, GLP-1 drugs could theoretically both reduce viral entry and control the damaging immune overreaction that makes COVID-19 severe.

Why did critical care patients respond differently than milder cases?

In critically ill patients, the disease had already progressed to a point where massive inflammation and organ damage were underway. The low-dose liraglutide may not have been enough to counteract this advanced inflammatory cascade. In milder cases, the drug was given earlier when the immune system was still manageable, potentially allowing liraglutide's anti-inflammatory and CD147-lowering effects to have a meaningful impact.

Read the original research

Early Use of Liraglutide for the Treatment of Acute COVID-19 Infection: An Open-Label Single-Center Phase II Safety Study with Biomarker Profiling.

Infectious disease reports, 17(1)

View on PubMed ↗Publisher’s paper ↗

Citation

Ferreira, Eloara V M; Oliveira, Rudolf K F; Salomao, Reinaldo; Brunialti, Milena K C; Cardoso, Martyella B A; Chen, Chien-Nien; Zhao, Lan; McCabe, Colm. (2025). Early Use of Liraglutide for the Treatment of Acute COVID-19 Infection: An Open-Label Single-Center Phase II Safety Study with Biomarker Profiling.. Infectious disease reports, 17(1). https://doi.org/10.3390/idr17010005