https://doi.org/10.1007/s00392-025-02625-4
Nadim Tabaza (Aachen)1, M. Reugels (Aachen)1, B. Kurt (Aachen)1, J. Spießhöfer (Aachen)2, P. Balfanz (Aachen)1, B. Hartmann (Aachen)1, S. F. Mause (Aachen)1, A. Milzi (Aachen)1, K. Kneizeh (Aachen)1, J. Schröder (Aachen)1, A. Kersten (Aachen)1, D. Müller-Wieland (Aachen)1, G. Marx (Aachen)3, M. Dreher (Aachen)1, N. Marx (Aachen)1, M. Lehrke (Traunstein)4, F. Kahles (Aachen)1
1Uniklinik RWTH Aachen
Med. Klinik I - Kardiologie, Angiologie und Internistische Intensivmedizin
Aachen, Deutschland; 2Uniklinik RWTH Aachen
Med. Klinik V - Klinik für Pneumologie und Internistische Intensivmedizin
Aachen, Deutschland; 3Uniklinik RWTH Aachen
Klinik für Operative Intensivmedizin und Intermediate Care
Aachen, Deutschland; 4Klinikum Traunstein
Kardiologie
Traunstein, Deutschland
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.