Journal of virologyJul 9, 2026

Glucagon-like peptide-1 receptor agonist may prevent lung scarring after COVID-19 in people with type 2 diabetes

Long Covid Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jul 10, 2026

Abstract

People with type 2 diabetes exhibited significantly upregulated fibrosis-related genes in monocytes after SARS-CoV-2 infection.

Upregulation of fibrosis-related genes in monocytes positively correlated with pulmonary fibrosis biomarkers up to 3 months post-infection.
In db/db mice modeling human type 2 diabetes, SARS-CoV-2 infection also led to increased fibrosis-related gene expression in lung macrophages.
Persistent pulmonary fibrosis was observed in db/db mice following SARS-CoV-2 infection.
Pro-inflammatory macrophages in db/db mice were identified as key factors contributing to pulmonary fibrosis after infection.
Treatment with the anti-type 2 diabetes drug GLP1-RA normalized fibrosis-related gene expression and significantly reduced pulmonary fibrosis.

Simplified

Post-acute sequelae of COVID-19 (PASC) poses a major health burden after SARS-CoV-2 infection. Although type 2 diabetes (T2D) is associated with PASC, the mechanism of T2D-mediated PASC in the lung remains elusive. Here, we found that people with T2D (PWT2D) exhibited significantly upregulated fibrosis-related genes in monocytes, which positively correlated with pulmonary fibrosis-related biomarkers up to 3 months after acute SARS-CoV-2 infection. Using db/db mice to model human T2D, we found consistently that SARS-CoV-2 infection resulted in upregulation of fibrosis-related genes in lung macrophages and persistent pulmonary fibrosis. Moreover, the macrophage-depletion demonstrated that pro-inflammatory macrophages in db/db mice were determinants for inducing pulmonary fibrosis post-infection. Importantly, the anti-T2D glucagon-like peptide-1 receptor agonist (GLP1-RA) reprogramed macrophage responses to SARS-CoV-2 by normalizing fibrosis-related genes, significantly reducing the pulmonary fibrosis in a glucose-independent manner. These findings demonstrated that SARS-CoV-2-induced proinflammatory macrophages are detrimental factors in T2D-mediated PASC, which can be prevented by GLP1-RA.