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They mimic the action of GLP-1 to reduce glucose levels through stimulation of insulin secretion and inhibition of glucagon secretion. They also reduce body weight by inducing satiety through central actions. The GLP-1 receptor agonists used clinically are based on exendin-4 and native GLP-1 and are available as formulations for daily or weekly s.c. or oral administration. GLP-1 receptor agonism is also achieved by inhibitors of dipeptidyl peptidase-4 (DPP-4), which prevent the inactivation of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), thereby prolonging their raised levels after meal ingestion. Other developments in GLP-1 receptor agonism include the formation of small orally available agonists and compounds with the potential to pharmaceutically stimulate GLP-1 secretion from the gut. In addition, GLP-1\/glucagon and GLP-1\/GIP dual receptor agonists and GLP-1\/GIP\/glucagon triple receptor agonists have shown the potential to reduce blood glucose levels and body weight through their effects on islets and peripheral tissues, improving beta cell function and stimulating energy expenditure. This review summarises developments in gut hormone-based therapies and presents the future outlook for their use in type 2 diabetes and obesity.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s00125-023-05929-0","type":"journal-article","created":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T02:02:20Z","timestamp":1684548140000},"page":"1796-1808","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":91,"title":["Gut hormone-based pharmacology: novel formulations and future possibilities for metabolic disease therapy"],"prefix":"10.1007","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4744-371X","authenticated-orcid":false,"given":"Matthias","family":"Tsch\u00f6p","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9976-9930","authenticated-orcid":false,"given":"Ruben","family":"Nogueiras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9804-5340","authenticated-orcid":false,"given":"Bo","family":"Ahr\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,5,20]]},"reference":[{"key":"5929_CR1","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1042\/bj0010028","volume":"1","author":"B Moore","year":"1906","unstructured":"Moore B, Edie ES, Abram JS (1906) On the treatment of diabetes mellitus by acid extract of duodenal mucous membrane. 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He was a member of the Research Cluster Advisory Panel (ReCAP) of the Novo Nordisk Foundation between 2017 and 2019. He attended a scientific advisory board meeting of the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, in 2016. He received funding for his research projects from Novo Nordisk (2016\u20132020) and Sanofi-Aventis (2012\u20132019). He has been a consultant for Bionorica (2013\u20132017), Menarini Ricerche (2016) and Bayer Pharma AG Berlin (2016). As former Director of the Helmholtz Diabetes Center and the Institute for Diabetes and Obesity at Helmholtz Zentrum M\u00fcnchen (2011\u20132018) and, since 2018, as CEO of Helmholtz Zentrum M\u00fcnchen, he has been responsible for collaborations with a multitude of companies and institutions worldwide. In this capacity, he discussed potential projects with and has signed\/signs contracts for his institute(s) and for the staff for research funding and\/or collaborations with industry and academia worldwide, including, but not limited to, pharmaceutical corporations such as Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Medigene, Arbormed and BioSyngen. In this role, he was\/is further responsible for commercial technology transfer activities of his institute(s), including diabetes-related patent portfolios of Helmholtz Zentrum M\u00fcnchen, for example WO\/2016\/188,932 A2 and WO\/2017\/194,499 A1. BA has served as a speaker for Novo Nordisk during the last 12 months and owns stocks in Novo Nordisk, which produces GLP-1 receptor agonists. BA was also a member of the board of Novo Nordisk Foundation between 2006 and 2017. RN declares that there are no relationships or activities that might bias, or be perceived to bias, his work.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 relationships and activities"}},{"value":"All authors were responsible for drafting the article and revising it critically for important intellectual content. All authors approved the version to be published.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}