[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-433951-105":59,"doc-detail-433951-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","nutrient-stimulated-hormone-based-therapies-transforming-obesity-management","Nutrient-Stimulated Hormone-Based Therapies - Transforming Obesity Management","","Nutrient-stimulated hormone (NuSH) pathway–targeting therapies are presented as a major shift in obesity management. While lifestyle modification remains foundational, limited durability drives the need for adjunct pharmacotherapy. The review contrasts older appetite- or fat-absorption–focused drugs with incretin-based agents that coordinate effects on satiety, gastric motility, insulin signaling, and cardiometabolic regulation. Evidence highlights substantial weight loss from injectable and next-generation multi-agonists, notes the importance of maintenance to prevent regain, and discusses emerging oral options and cardiovascular and liver-related risk reductions.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/nutrient-stimulated-hormone-based-therapies-transforming-obesity-management/433951/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/nutrient-stimulated-hormone-based-therapies-transforming-obesity-management/433951.png","ImageObject",300,407,{"name":92,"@type":93},"Riley","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why are nutrient-stimulated hormone (NuSH) pathways considered transformative for obesity management?","Question",{"text":112,"@type":113},"NuSH-targeting therapies act on neurometabolic circuitry that regulates appetite, nutrient sensing, and energy homeostasis, leading to more coordinated control of obesity than approaches limited to appetite or fat absorption.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do newer incretin-based therapies compare with conventional anti-obesity drugs?",{"text":117,"@type":113},"Older agents were largely designed to reduce appetite or inhibit fat absorption and typically show only modest efficacy with adverse-effect limitations, whereas incretin-based drugs mimic endogenous postprandial hormones to improve satiety, insulinotropic signaling, and cardiometabolic regulation.",{"name":119,"@type":110,"acceptedAnswer":120},"Why is maintenance therapy important in obesity pharmacotherapy?",{"text":121,"@type":113},"Long-term findings indicate that discontinuation often causes substantial weight regain, reflecting obesity’s chronic, relapsing nature and the need for sustained treatment.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},433951,1791265199,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":19,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":52,"preview_page_count":4},1374391975076,"https://ap-avatar.wpscdn.com/avatar/14000253ca4ec9f6853?x-image-process=image/resize,m_fixed,w_180,h_180&k=1783305029341752051","Editorial  \nEndocrinol Metab 2025;40:879-882 [https://doi.org/10.3803/EnM.2025.2803](https://doi.org/10.3803/EnM.2025.2803)[ ](https://doi.org/10.3803/EnM.2025.2803)[pISSN 2093-596X](pISSN 2093-596X) · eISSN 2093-5978  \nNutrient-Stimulated Hormone-Based Therapies: Transforming Obesity Management  \nKi Hoon Kwak1,2, Chang Hee Jung1,2  \n1Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine; 2Asan Diabetes Center, Asan Medical Center, Seoul, Korea  \nObesity is a chronic, relapsing, and heterogeneous metabolic disease that increases the risk of type 2 diabetes, cardiovascular disease, metabolic dysfunction-associated steatotic liver disease (MASLD), and several obesity-related cancers [1] . Although lifestyle modification remains the cornerstone of therapy, its limited long-term durability necessitates adjunctive pharmacotherapy [2] . Recent therapeutic advances, particularly those that harness nutrient-stimulated hormonal (NuSH) pathways, have fundamentally transformed obesity management by targeting the neurometabolic circuitry that underlies dysregulated appetite, impaired nutrient sensing, and disrupted energy homeostasis [3] .  \nConventional pharmacological agents, such as orlistat (a gastrointestinal lipase inhibitor), naltrexone/bupropion, and phentermine/topiramate, were largely designed to reduce appetite or inhibit fat absorption [4]. Although these medications are effective for some individuals, they generally provide only modest efficacy, and their adverse effect profiles have limited broader clinical adoption [4] . In contrast, incretin-based agents—most notably glucagon-like peptide-1 (GLP-1) receptor agonists and dual GLP-1/glucose-dependent insulinotropic peptide (GIP) agonists—mimic key components of the endogenous postprandial hormonal milieu and exert integrated effects on satiety, gastric motility, insulinotropic signaling, and cardiometabolic regulation [5] . Semaglutide 2.4 mg, the most recent single peptide targeting the GLP-1 receptor, produces approximately 15% weight  \nreduction over 68 weeks [6], whereas tirzepatide, a dual GLP-1/ GIP agonist, achieves nearly 20% reductions [7], approaching outcomes typically observed with bariatric procedures. However, long-term studies highlight the importance of maintenance therapy, as discontinuation frequently leads to substantial weight regain [8], reflecting the chronic and relapsing nature of obesity and the need for sustained intervention.  \nThe therapeutic horizon continues to expand with next-generation poly-agonists that integrate complementary receptor mechanisms. Dual GLP-1/glucagon agonists such as survodutide augment lipid oxidation and energy expenditure [9], while GLP-1/amylin combinations (e.g., CagriSema, Novo Nordisk, Bagsværd, Denmark) enhance satiety through convergent hypothalamic and area postrema pathways [10] . Triple agonists, exemplified by retatrutide, which targets GLP-1, GIP, and glucagon receptors simultaneously, have produced weight reductions exceeding 24% in phase 2 trials [11], signaling a potential shift toward pharmacological outcomes that parallel metabolic surgery. These peptide-engineered agents leverage extended halflife designs, optimized receptor-affinity ratios, and balanced intracellular signaling to achieve multi-axis metabolic modulation.  \nIn parallel with the rapid development of peptide-based incretin agonists, the emergence of oral small-molecule incretin mimetics represents a significant inflection point in the field. Although injectable GLP-1 receptor agonists remain the standard  \nReceived: 19 November 2025, Accepted: 24 November 2025  \nCorresponding author: Chang Hee Jung  \nDepartment of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea Tel: +82-2-3010-1418, Fax: +82-2-3010-3710, E-mail: [chjung0204@gmail.com](chjung0204@gmail.com)  \nCopyright © 2025 Korean Endocrine Society  \nThis is an Open A","cbCaie0BCPFJjtdT","https://ap.wps.com/l/cbCaie0BCPFJjtdT","pdf",505029,"English","# Nutrient-stimulated hormone (NuSH) strategies in obesity\n## Limitations of lifestyle and older pharmacotherapy\n## Incretin-based agents and maintenance therapy\n## Next-generation multi-agonists and oral incretin mimetics\n## Cardiometabolic benefits and guideline implications","[{\"question\":\"Why are nutrient-stimulated hormone (NuSH) pathways considered transformative for obesity management?\",\"answer\":\"NuSH-targeting therapies act on neurometabolic circuitry that regulates appetite, nutrient sensing, and energy homeostasis, leading to more coordinated control of obesity than approaches limited to appetite or fat absorption.\"},{\"question\":\"How do newer incretin-based therapies compare with conventional anti-obesity drugs?\",\"answer\":\"Older agents were largely designed to reduce appetite or inhibit fat absorption and typically show only modest efficacy with adverse-effect limitations, whereas incretin-based drugs mimic endogenous postprandial hormones to improve satiety, insulinotropic signaling, and cardiometabolic regulation.\"},{\"question\":\"Why is maintenance therapy important in obesity pharmacotherapy?\",\"answer\":\"Long-term findings indicate that discontinuation often causes substantial weight regain, reflecting obesity’s chronic, relapsing nature and the need for sustained treatment.\"}]","Nutrient-Stimulated Hormone-Based Therapies - Transforming Obesity Management | PDF",1790666366]