Abstract
BACKGROUND: Glucagon-like peptide-1 (GLP-1) agonists are an existing treatment option for patients with insulin-resistant states, which elicit further pleiotropic effects related to immune cell recruitment and vascular inflammation. GLP-1 agonists downregulate the cluster of differentiation 147 (CD147) receptor, one of several receptors for the SARS-CoV-2 spike protein that mediate viral infection of host cells. METHODS: We conducted an open-label prospective safety and tolerability study including biomarker responses of the GLP-1 agonist Liraglutide, administered for 5 days as an add-on therapy to the standard of care within 48 h of presentation in a cohort of 13 patients hospitalized with COVID-19 pneumonia. Biomarker responses were compared in patients admitted to critical care and those not requiring critical care admission (non-critical group). RESULTS: Liraglutide (0.6 mg, subcutaneously) was well tolerated by all patients and all patients were alive 30 days after diagnosis. Plasma soluble CD147 levels were reduced in the non-critical patient group at day 5 in contrast to critical care-treated patients, who demonstrated an increase in soluble CD147 levels between day 0 and day 5. Patients with milder COVID-19 pneumonia severity also demonstrated improvement in echocardiographic parameters of right and left ventricular function, reduction in plasma Troponin levels, increased CD147 expression on T lymphocytes, and reduction in plasma IL-8. CONCLUSIONS: This first-in-disease use of the GLP-1 agonist Liraglutide demonstrates its safety and tolerability in an unselected cohort of patients hospitalized with COVID-19 pneumonia across a range of clinical severities.