Glucose-dependent insulinotropic polypeptide levels are independently associated with all-cause mortality in patients with obesity

R. Dettori (Aachen)¹, M. Reugels (Aachen)¹, M. Rau (Aachen)¹, S. Just (Aachen)¹, J. Möllmann (Aachen)¹, J. Spießhöfer (Aachen)², A. Milzi (Lugano)³, K. Kneizeh (Aachen)¹, M. Sausen (Aachen)¹, N. Tabaza (Aachen)¹, L. Quintana (Aachen)¹, N. Ganesh (Aachen)¹, M. Neuhaus (Aachen)¹, K. Müser (Aachen)¹, R. Salagundi (Aachen)¹, A. Kapoor (Aachen)¹, K. Thiele (Aachen)¹, E. Dahl (Aachen)⁴, J. Schröder (Aachen)¹, N. Marx (Aachen)¹, M. Lehrke (Traunstein)⁵, B. Kurt (Aachen)¹, 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; ³Istituto Cardiocentro Ticino - EOC Lugano, Schweiz; ⁴Uniklinik RWTH Aachen RWTH cBMB am Institut für Pathologie Aachen, Deutschland; ⁵Klinikum Traunstein Kardiologie Traunstein, Deutschland

Background: Obesity is a chronic life-threatening disease with more than one billion people affected worldwide. Patients with obesity face an increased risk of cardiovascular (CV) events and a reduction of life expectancy. Incretin-based therapies lead to substantial weight loss in patients with obesity and recently became available in clinical practice. Glucagon-like peptide-1 receptor agonists (GLP-1RA) were found to reduce CV events beyond weight loss and glucose lowering. CV outcomes trials with tirzepatide, a dual receptor agonist of GLP-1 and GIP (glucose-dependent insulinotropic polypeptide), in patients with obesity are ongoing. The role of GIP for CV risk in patients with obesity is not well understood. This study aims to investigate the prognostic value of endogenous GIP levels in patients with obesity.

Methods: We measured circulating admission total GIP levels in 231 stable patients with obesity (BMI >30kg/m², mean age 67.7 years) who presented with clinical indication of coronary angiography.

Results: Mean follow up time of our study was 3.4 years and the primary outcome was all-cause mortality. Kaplan-Meier plots showed that higher vs. lower baseline GIP levels (median: 306 pg/mL) were associated with higher mortality. This association remained significant after adjustment for age, sex, BMI, diabetes and CKD (HR 1.98 [1.16 - 3.37]; p=0.001).

Conclusion: Higher GIP levels are independently associated with all-cause mortality in patients with obesity who presented with indication of coronary angiography. Future larger studies are needed to investigate underlying mechanisms and clinical relevance of these findings.