AUTHOR=Andrade Sara , Lobato Carolina B. , Machado Mariana , Hartmann Bolette , Holst Jens J. , Almeida Rui F. , Nora Mário , Monteiro Mariana P. , Guimarães Marta , Pereira Sofia S. TITLE=GLP-1 and GIP may play a role in long-term weight trajectories after gastric bypass JOURNAL=Frontiers in Endocrinology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1624001 DOI=10.3389/fendo.2025.1624001 ISSN=1664-2392 ABSTRACT=IntroductionSuboptimal 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).MethodsThis 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). ResultsFasting 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.DiscussionIn 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.