GLP-1 and GIP may play a role in long-term weight trajectories after gastric bypass

Introduction: Suboptimal clinical responses to metabolic and bariatric surgery include insufficient weight loss (WL), weight regain (WR), and/or comorbidity remission failure or relapse. Gut hormones' role in WR and Type 2 diabetes (T2D) relapse is not fully established. So, our aim was to evaluate the hormone profiles of patients with long-term optimal and suboptimal response after gastric bypass (RYGB). Methods: This cross-sectional study included 43 individuals who underwent RYGB surgery over 10 years ago, divided into two groups: 23 participants with no T2D history but different WR trajectories (cohort 1), and 20 with prior T2D diagnosis and optimal WL (cohort 2), with post-RYGB T2D remission (n=10) or relapse (n=10). Results: Fasting and postprandial glucose, insulin, C-peptide, glucagon, GLP-1 and GIP levels were evaluated during a mixed-meal tolerance test. In cohort 1, fasting glucose, insulin, C-peptide, and glucagon, as well as the postprandial glucose and GIP levels, were significantly positively correlated with %WR. Additionally, postprandial GLP-1 and glucagon levels were negatively correlated with the %WR. In cohort 2, higher postprandial glucose and lower insulin were observed in participants with T2D relapse. No other significant differences were observed. Discussion: In sum, greater WR was associated with higher levels of postprandial glucose and GIP, along with lower GLP-1 and glucagon excursions. Whether these are cause or consequence of WR remains to be clarified. Additionally, GIP and GLP-1 profile of participants with T2D relapse did not differ from those with T2D remission.