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. 2025 Jul 4:16:1624001.
doi: 10.3389/fendo.2025.1624001. eCollection 2025.

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

Sara Andrade  1   2 , Carolina B Lobato  1   2   3   4 , Mariana Machado  1   2 , Bolette Hartmann  3 , Jens J Holst  3   5 , Rui F Almeida  6 , Mário Nora  6 , Mariana P Monteiro  1   2 , Marta Guimarães  1   2   6 , Sofia S Pereira  1   2
Affiliations

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

Sara Andrade et al. Front Endocrinol (Lausanne). .

Abstract

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.

Keywords: RYGB; T2D relapse; enteropancreatic hormones; suboptimal long-term outcomes; weight regain.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Correlations between % total weight loss (%TWL) and % weight regain (%WR) with fasting and postprandial (iAUC) levels of glucose, insulin, and C-peptide, as well as insulin secretion rate (ISR), markers of beta-cell function (HOMA2-B), peripheral insulin sensitivity (HOMA2-S), insulin resistance (HOMA2-IR), insulin clearance, oral glucose insulin sensitivity (OGIS), insulinogenic index (IGI), and disposition index. Only patients with no Type 2 diabetes history were included (Cohort 1, n=23). Pearson correlation test: colored cells indicate statistically significant positive (green) or negative (red) correlations between the variables.
Figure 2
Figure 2
Peripheral levels of glucose (A), insulin (B), C-peptide (C), glucagon-like peptide 1 [GLP-1, (D)], glucose-dependent insulinotropic polypeptide [GIP, (E)] and Glucagon (F) in response to a mixed meal tolerance test in patients with Type 2 diabetes remission or relapse after remission (Cohort 2, n=10 per group). Data is presented as mean ± SD. Two-way ANOVA with Sidak’s post hoc test: No significant differences observed.
Figure 3
Figure 3
Correlations between % total weight loss (%TWL) and % weight regain (%WR) with fasting and postprandial (iAUC) levels of glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon. Pearson correlation test: colored cells indicate statistically significant positive (green) or negative (red) correlations between the variables.
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