Society: AGA
Background: Sound evidence support the effectiveness of the transoral outlet reduction (TORe) with full-thickness endoscopic suturing (FTS) or argon plasma coagulation (APC) alone to address post-RYGB weight regain. Although clinically effective, its effects on gut hormone dynamics and their relationship with weight loss and clinical success rates are still unknown, demanding an investigation.
Methods: This is a substudy of a previous randomized clinical trial. Adult patients with post-RYGB significant weight regain and dilated GJA underwent TORe with APC alone or APC plus FTS (FTS-APC). Serum levels of ghrelin, GLP-1, and PYY were measured at fasting, 30, 60, 90, and 120 minutes after a standardized liquid meal. We used the Student T-test to compare continuous variables and the analysis of variance for repeated measures to analyze and compare the variation of hormonal levels over time. A p-value<.05 was considered statistically significant for a 95% confidence interval.
Results: Thirty-six patients (19 APC vs. 17 FTS-APC) successfully underwent blood sampling at baseline and 12 months (90% follow-up rate). There was no significant baseline difference between patients according to allocation group, history of cholecystectomy, or clinical success (≥10%TWL at 12 months) – Table 1. In all analyses, the typical postprandial decrease in ghrelin levels was delayed by 30 minutes. Other than that, no significant changes in ghrelin levels were noted. GLP-1 levels significantly decreased at 12 months in both allocation groups. We noted similar findings when splitting the sample according to the history of cholecystectomy and clinical success. The APC group presented an increase in PYY levels at 90 minutes, while FTS-SPC did not. The area under the curve between 30-120 minutes significantly increased in the first group (p=0.02) but did not change in the latter (p=0.41). When splitting the sample according to the history of cholecystectomy, we noted that naïve patients had significantly lower PYY levels at baseline (p=0.01). Moreover, cholecystectomized patients experienced a significant increase in the AUC for PYY levels, while naïve patients did not, leading to a higher AUC at 12 months in the former group (p=0.0001). PYY levels and behavior over time were similar when comparing clinical success and failure cases. There was no significant association between the allocation group and the history of cholecystectomy (p=0.053), meaning that both variables independently influence the changes in PYY levels.
Conclusions: Our findings collectively suggest that APC-TORe triggers a more pronounced enteroendocrine response, especially in cholecystectomized patients. GLP-1 levels decrease after TORe, despite the technique employed. Opportunistically, prescribing GLP-1 analogs routinely seems reasonable to further enhance the hormonal response after TORe.

Figure 1 – Demographic characteristics according to allocation group, clinical success, and history of cholecystectomy.
Figure 2 – Graphs showing behavior over time of Ghrelin, GLP-1, and PYY levels at baseline and at 12 months.