GLP-1s May Curb Lung Fibrosis in Diabetes, Long COVID

A glucagon-like peptide-1 receptor agonist (GLP-1 RA) prevented pulmonary fibrosis in a mouse model of type 2 diabetes (T2D) following SARS-CoV-2 infection, according to findings published in the Journal of Virology. The effect appeared to work independently of glucose lowering, pointing toward an anti-inflammatory mechanism that could eventually matter for the roughly 1 in 10 patients who develop lung-related postacute sequelae of COVID-19 (PASC).

For pharmacists already managing GLP-1 RA therapy in patients with T2D, the work adds another dimension to a drug class whose nonglycemic effects continue to expand—though these are animal data, and nothing here changes practice today.¹

Why Patients With Diabetes Face Higher Risk

The incidence of pulmonary PASC among people with T2D is 4 times higher than among those without T2D, and the immune mechanisms behind that gap have remained poorly characterized. Investigators at the University of Hong Kong first reanalyzed a previously published single-cell RNA sequencing data set from patients hospitalized with COVID-19, comparing those with T2D (n = 11) against those without (n = 79) across 3 timepoints: hospital admission, acute disease around 5 days postadmission, and convalescence 2 to 3 months following symptom onset.¹

Patients with T2D showed significantly upregulated fibrosis-related genes in monocytes—including cathepsin D, HIF-1α, and lactate dehydrogenase A—that correlated positively with pulmonary fibrosis biomarkers at the convalescent timepoint.¹

Macrophages as the Driver

Using db/db mice as a T2D model, the team found that SARS-CoV-2 infection produced persistent lung fibrosis and long-lasting weight loss not seen in nondiabetic controls. Depleting pulmonary macrophages with clodronate liposomes significantly reduced collagen deposition and improved weight recovery, establishing proinflammatory macrophages as determinants of the fibrotic response rather than bystanders.¹

Study leader Runhong Zhou, PhD, assistant professor at Hong Kong University’s School of Clinical Medicine Department of Microbiology, noted that people with diabetes experience far more severe infection-related disease after COVID-19 than others and that the team wanted to understand the source of those long-term symptoms.²

What the GLP-1 RA Did

Mice received daily intraperitoneal injections of a GLP-1-Fc construct or control-Fc from day 1 through day 14 postinfection. Treatment reduced diffuse alveolar damage, decreased α-smooth muscle actin production, and prevented collagen deposition in the lungs at 15 days postinfection. Critically, nonfasting blood glucose fell only nonsignificantly, supporting a glucose-independent antifibrotic effect.¹

Mechanistically, the GLP-1 RA appeared to reprogram bone marrow-derived macrophages, restoring CXCL10 induction that was absent in infected diabetic mice and suppressing the fibrosis genes cathepsin D and lactate dehydrogenase A. The GLP-1 receptor is highly expressed in lung tissue, which the authors cite as a plausible route for local activity.¹

Context for Pharmacists

This is not the first antidiabetic agent linked to PASC prevention. In the COVID-OUT trial, outpatient metformin reduced long COVID incidence by approximately 41% versus placebo over 300 days, with a cumulative incidence of 6.3% versus 10.4%. More recent ACTIV-6 data reinforced that signal. Because metformin increases endogenous GLP-1 secretion, the study authors speculate the mechanisms may overlap.^3,4

Pharmacists fielding questions about GLP-1 RAs and long COVID should be clear about the evidentiary ceiling here. In an interview with Pharmacy Times, Zhou characterized the findings as preliminary proof of concept involving a small number of mice. The construct tested was a GLP-1-Fc fusion protein produced in-house, not semaglutide (Ozempic, Wegovy; Novo Nordisk), tirzepatide (Zepbound, Mounjaro; Eli Lilly), or any marketed agent, and no dosing inference to human products is supported.^1,2

“Whether this approach would also benefit people with T2D who have good glycemic control remains unknown,” Zhou explained. “Currently, a phase 2 clinical trial is evaluating a GLP‑1 agonist for long COVID, and its results will have important clinical implications.”

The authors also note that longer-term studies are needed to assess sustained antifibrotic effects and that combinations with metformin or SGLT2 inhibitors remain untested.¹

“Current evidence suggests that antidiabetic therapy may influence COVID-19-related outcomes, but it is not yet strong enough to use such therapy as a stand-alone reason to change treatment in patients presenting with acute COVID-19,” Zhou noted. “These proof-of-concept findings should next be validated in non-human primate models and then tested in clinical trials.”

For now, the practical takeaway is counseling accuracy: patients with T2D carry an elevated risk of persistent respiratory symptoms after COVID-19, and adherence to existing therapy plus vaccination remains the evidence-based intervention.¹

REFERENCES

1. Zhou R, Yue M, Shen Q, et al. Glucagon-like peptide-1 receptor agonist prevents pulmonary fibrosis following acute COVID-19 infection associated with type 2 diabetes. J Virol. 2026;0:e00401-26. doi:10.1128/jvi.00401-26

2. GLP-1 agonists may help people with diabetes and long COVID. American Society for Microbiology. News release. July 9, 2026. Accessed July 22, 2026. https://www.eurekalert.org/news-releases/1135006

3. Bramante CT, Buse JB, Liebovitz DM, et al. Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial. Lancet Infect Dis. 2023;23(10):1119-1129. doi:10.1016/S1473-3099(23)00299-2

4. Ferruggia K. Metformin cuts long COVID risk by 50%, new trial confirms. Pharmacy Times. June 17, 2026. Accessed July 22, 2026. https://www.pharmacytimes.com/view/metformin-cuts-long-covid-risk-by-50-new-trial-confirms