Society: AGA

Background: Transoral outlet reduction endoscopy (TORe) has been shown to be effective in managing weight regain after Roux-en-Y gastric bypass (RYGB), as has the glucagon-like peptide-1 agonist, liraglutide. However, the effect of adjunctive liraglutide after TORe has yet to be assessed. Herein, we evaluate the efficacy of liraglutide treatment when initiated immediately post-TORe or one year post-TORe using a crossover study design.

Methods: This was a retrospective study of prospectively collected data from a double-blinded randomized controlled trial. Participants underwent TORe at three outpatient clinics in São Paulo, Brazil, between December 2018 and December 2022. Two participant cohorts were established. Participants in the placebo-first cohort, “group A,” underwent the TORe procedure and received subcutaneous saline solution. Those in the liraglutide-first cohort, “group B,” initiated subcutaneous liraglutide immediately after the revisional TORe procedure. The average liraglutide dose was 1.8 mg. Participants were dosed weekly for 12 months, at which point crossover occurred. Each participant received placebo and liraglutide for equal duration over the 24-month treatment phase. All participants had their diet and exercise regimens prescribed by the same multidisciplinary team. TORe technique and post-procedure follow-up were identical at all sites. Primary outcomes were percent total body weight loss (%TBWL) 12 and 24 months after treatment initiation. The secondary outcome was change in hepatic steatosis using the Brunt score.

Results: This study included 58 participants in group A and 51 participants in group B. There was no significant difference in mean baseline BMI. Participants in group A had significantly lower %TBWL than those in group B at 6, 9, and 12 months (p<0.001 at each timepoint). After crossover, no significant difference in %TBWL was observed between groups at 15 and 18 months. Group B continued to show greater %TBWL than group A at 21 and 24 months, despite previously discontinuing liraglutide (p<0.001 for both timepoints). Those in group A, who received placebo first, had significantly higher steatosis scores at 12 months compared with those in group B (p<0.05). This between-group difference in steatosis score was eliminated by 24 months.

Conclusions: Immediate post-procedure administration of liraglutide may be superior to placebo in reversing weight regain and in improving hepatic steatosis for patients undergoing revisional TORe. Our study is the first to demonstrate that the timing of post-TORe liraglutide initiation may improve therapeutic benefit of the procedure. Further inquiry is necessary to elucidate the physiologic basis of this observed effect.

Enad Dawod

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