Background: Glucagon-like peptide 1 (GLP-1) is a gut incretin hormone, which induces post-prandial glucose-dependent insulin secretion. GLP-1 receptor agonists (GLP-1RA) were found to reduce atherosclerosis and vascular inflammation and improved cardiovascular outcomes in patients with diabetes or obesity at high cardiovascular risk. Interestingly treatment with GLP-RA was associated with improved outcomes in patients with COVID-19. The aim of this study was to investigate the role of endogenous circulating GLP-1 in patients with COVID-19.
Methods: We performed serial plasma GLP-1 measurements (at time of admission, week 1, week 2 and week 6) in 119 patients with COVID-19 at University Hospital Aachen (02/2020 – 01/2021). The primary outcome of the study was all-cause mortality.
Results: At baseline mean age was 65 years, 69% were male, mean BMI was 30.7 kg/m2, 37% of the participants had diabetes, 61% presented with ARDS and 29% had coronary artery disease. Circulating GLP-1 at baseline and week 1 was higher in non-survivors (baseline: 120.69 pM, σ 97.39, n=34; week 1: 149.71 pM, σ 115.48, n=27) compared to survivors (baseline: 70.94 pM, σ 56.53,n=85; week 1: 77.65 pM, σ 69.27, n=67, p<0.05). Kaplan-Meier survival plots (separated by increasing quartiles with GLP-1 cut-off values of 33,76 pM; 59,19 pM; 122,44 pM; 380,79 pM) and mutlivariable cox regression analyses adjusted for age and sex found GLP-1 to be associated with mortality (Chi2: 9.97; p=0.002). T2e association of baseline GLP-1 with mortality remained significant after adjustment for age, sex, eGFR, lactate and diabetes (Chi2: 20.23; p=0.002). Addition of GLP-1 on top of the Sequential Organ Failure Assessment (SOFA) Score provided significant incremental added value and improved model performance (SOFA: Chi2: 9.24; AIC: 152.47; SOFA + GLP-1: Chi2: 15.33; AIC: 150.39; delta Chi2: 6.09; fraction of new information: 40%; p=0.0174).
Conclusion: These findings suggest that endogenous circulating GLP-1 is a strong, independent and clinically revant biomarker for mortality prediction in patients hospitalized due to COVID-19. Future studies are needed to investigate underlying mechanisms and potential therapeutical targets.
