Background and aims: Cardiovascular trials have revealed the positive impact of GLP-1 receptor agonists (GLP-1 RAs) on cardiovascular outcomes in type 2 diabetes (T2D). However, the specific effects of endogenous GLP-1 on arterial stiffness and renal function remain understudied. This study aimed to explore the influence of endogenous GLP-1 response after Gastric Bypass (RYGB) on arterial stiffness and renal hemodynamic. Materials and methods: Thirty individuals with morbid obesity and pre-diabetes scheduled for RYGB, were included. Pre-diabetes was defined according to ADA guidelines. Clinical and diagnostic assessments both before and 1-year post-surgery were performed. The assessment included 3-hours oral glucose tolerance test (OGTT) with serial sampling for glycemia, GLP-1 and insulin as well as carotid-femoral pulse wave velocity (cf-PWV), ultrasound images of carotid for assessing distensibility coefficient (DC) and Young’s elastic modulus, along with measurement of renal resistive index (RRI). Participants were categorized into High-Response and Low-Response groups based on their post-surgery increase in GLP-1 (median increase of 100% and 1%, respectively, pre- vs post-surgery). Results: Baseline anthropometric and glucometabolic characteristics between the groups were similar, except for slightly higher eGFR levels in the High-Response group (p=0.032). Following surgery, both groups experienced significant reductions in BMI, fasting glycemia, and fasting insulin levels, with no notable differences between the groups. Interestingly, the carotid distensibility coefficient (DC) notably improved more in the High-Response group post-surgery (p int=0.039). The renal resistive index (RRI) decreased significantly only in the High-Response group, remaining stable in the Low-Response group. Additionally, cf-PWV decreased in both groups, with a more significant reduction observed in the High-Response group (p int=0.031). Finally, a stepwise regression analysis indicated that the percentage increase in GLP-1 was the best predictor of the percentage decrease in cf-PWV (p=0.014), even after including the variation in mean blood pressure and BMI as covariates. Conclusions: elevated endogenous GLP-1 response following RYGB was associated with improved arterial stiffness and RRI, suggesting cardio-renal benefits. The findings underscore the potential role of endogenous GLP1 in influencing vascular hemodynamics independent of traditional weight loss.