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

IF 5.7 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes, Obesity & Metabolism Pub Date : 2025-09-30 DOI:10.1111/dom.70167

Sara Russo, Luca Proto, Manoel Galvao Neto, Giulia Angelini, Samantha Pezzica, Fabrizia Carli, Elena Previti, Maria Emiliana Caristo, Vincenzo Bove, Rima Chakaroun, Sara Roggiani, Valentina Tremaroli, Carel W Le Roux, Stefan R Bornstein, Amalia Gastaldelli, Ivo Boskoski, Geltrude Mingrone

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引用次数: 0

Abstract

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 (S_I). 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. S_I, insulin secretion, glucose rate of appearance (R_a), metabolomics, and faecal microbiota were analysed.

Results: ForePass improved S_I more than Semaglutide (2.75 ± 0.37 vs. 1.34 ± 0.21 min^-1·pM^-1) and sham (0.78 ± 0.46; p <0.05). Weight gain was 2.0 kg (4%) with ForePass, versus 16.3 kg (36%) with Semaglutide and 21.1 kg (47%) with sham (p <0.0001). Semaglutide reduced weight gain by 11% versus sham (p <0.05). DI was 2.6-fold higher with ForePass than Semaglutide and 3.5-fold higher than sham. ForePass reduced oral glucose R_a by 40% versus Semaglutide and 30% versus sham, while EGP 46% was lower than Semaglutide and 51% lower than sham (p <0.0001). Metabolomics showed ForePass increased ketogenic and branched-chain amino acids, whereas Semaglutide raised lactate and alanine. Only ForePass increased faecal Akkermansia muciniphila.

Conclusions: ForePass produced superior insulin sensitivity and weight outcomes versus Semaglutide. Its distinct effects on glucose disposal, metabolomics, and microbiota support development as a reversible, incision-free endoscopic therapy that may bridge the gap between pharmacological and surgical options for obesity and type 2 diabetes.

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在猪的体重控制、葡萄糖代谢和肠道微生物群方面，ForePass优于Semaglutide。

目的：本研究评估了forepass（一种新型的、无切口的、可逆的、内窥镜下输送的模拟胆管胰腺转移的装置）在生长猪中的代谢功效。主要目的是ForePass在改善胰岛素敏感性（SI）方面优于Semaglutide。次要目的包括对体重增加、内源性葡萄糖生成（EGP）、处置指数（DI）、口服葡萄糖率、血浆代谢组学和粪便微生物群的影响。材料和方法：在30天的时间里，12头长白猪（46.7±1.1 kg）接受了ForePass、每周两次的Semaglutide或假内窥镜检查。对主要终点的样本量进行先验计算（Δ = 0.6 min-1·pM-1, SD = 0.3, α = 0.05, 80%功率），每组n = 4。监测体重，并用稳定同位素示踪剂口服葡萄糖耐量试验（OGTT）评估肝脏葡萄糖处置。分析SI、胰岛素分泌、外观葡萄糖率（Ra）、代谢组学和粪便微生物群。结果：与Semaglutide相比，ForePass改善SI（2.75±0.37 vs. 1.34±0.21 min-1·pM-1）和sham（0.78±0.46;p a）分别提高40%和30%，而EGP比Semaglutide低46%，比sham低51% (p)。其对葡萄糖处理、代谢组学和微生物群的独特作用支持其作为一种可逆的、无切口的内窥镜治疗方法的发展，可能弥合肥胖症和2型糖尿病的药物和手术选择之间的差距。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetes, Obesity & Metabolism 医学-内分泌学与代谢

CiteScore

10.90

自引率

6.90%

发文量

319

审稿时长

3-8 weeks

期刊介绍： Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.