ForePass outperforms Semaglutide in weight control, glucose metabolism, and gut microbiota in swine

Aims: This study evaluated the metabolic efficacy of ForePass-a novel, incision-free, reversible, endoscopically delivered device that mimics biliopancreatic diversion-in growing pigs. The primary aim was the superiority of ForePass over Semaglutide in improving insulin sensitivity (SI). Secondary aims included effects on weight gain, endogenous glucose production (EGP), disposition index (DI), oral glucose rate of appearance, plasma metabolomics, and faecal microbiota. Materials and methods: Over 30 days, 12 young Landrace pigs (46.7 ± 1.1 kg) received ForePass, twice-weekly Semaglutide, or sham endoscopy. Sample size was calculated a priori for the primary endpoint (Δ = 0.6 min-1·pM-1, SD = 0.3, α = 0.05, 80% power), yielding n = 4 per group. Body weight was monitored, and oral glucose tolerance testing (OGTT) with stable isotope tracers assessed hepatic glucose disposal. SI, insulin secretion, glucose rate of appearance (Ra), metabolomics, and faecal microbiota were analysed. Results: ForePass improved SI more than Semaglutide (2.75 ± 0.37 vs. 1.34 ± 0.21 min-1·pM-1) and sham (0.78 ± 0.46; p