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
{"title":"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。","authors":"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","doi":"10.1111/dom.70167","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>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<sub>I</sub>). Secondary aims included effects on weight gain, endogenous glucose production (EGP), disposition index (DI), oral glucose rate of appearance, plasma metabolomics, and faecal microbiota.</p><p><strong>Materials and methods: </strong>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<sup>-1</sup>·pM<sup>-1</sup>, 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<sub>I</sub>, insulin secretion, glucose rate of appearance (R<sub>a</sub>), metabolomics, and faecal microbiota were analysed.</p><p><strong>Results: </strong>ForePass improved S<sub>I</sub> more than Semaglutide (2.75 ± 0.37 vs. 1.34 ± 0.21 min<sup>-1</sup>·pM<sup>-1</sup>) 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<sub>a</sub> 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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7000,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"ForePass outperforms Semaglutide in weight control, glucose metabolism, and gut microbiota in swine.\",\"authors\":\"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\",\"doi\":\"10.1111/dom.70167\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aims: </strong>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<sub>I</sub>). Secondary aims included effects on weight gain, endogenous glucose production (EGP), disposition index (DI), oral glucose rate of appearance, plasma metabolomics, and faecal microbiota.</p><p><strong>Materials and methods: </strong>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<sup>-1</sup>·pM<sup>-1</sup>, 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<sub>I</sub>, insulin secretion, glucose rate of appearance (R<sub>a</sub>), metabolomics, and faecal microbiota were analysed.</p><p><strong>Results: </strong>ForePass improved S<sub>I</sub> more than Semaglutide (2.75 ± 0.37 vs. 1.34 ± 0.21 min<sup>-1</sup>·pM<sup>-1</sup>) 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<sub>a</sub> 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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":158,\"journal\":{\"name\":\"Diabetes, Obesity & Metabolism\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2025-09-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes, Obesity & Metabolism\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/dom.70167\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes, Obesity & Metabolism","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/dom.70167","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
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 <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 Ra 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.
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.
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