{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:07:36Z","timestamp":1791976056660,"version":"4.4.0"},"reference-count":120,"publisher":"Korean Diabetes Association","issue":"3","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["e-dmj.org"],"crossmark-restriction":true},"short-container-title":["Diabetes Metab J"],"published-print":{"date-parts":[[2025,5,1]]},"abstract":"<jats:p>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as blockbuster drugs for treating metabolic diseases. Glucagon-like peptide-1 (GLP-1) plays a pivotal role in glucose homeostasis by enhancing insulin secretion, suppressing glucagon release, delaying gastric emptying, and acting on the central nervous system to regulate satiation and satiety. This review summarizes the discovery of GLP-1 and the development of GLP-1RAs, with a particular focus on their central mechanisms of action. Human neuroimaging studies demonstrate that GLP-1RAs influence brain activity during food cognition, supporting a role in pre-ingestive satiation. Animal studies on hypothalamic feed-forward regulation of hunger suggest that cognitive hypothalamic mechanisms may also contribute to satiation control. We highlight the brain mechanisms of GLP-1RA-induced satiation and satiety, including cognitive impacts, with an emphasis on animal studies of hypothalamic glucagon-like peptide-1 receptor (GLP-1R) and GLP-1R-expressing neurons. Actions in non-hypothalamic regions are also discussed. Additionally, we review emerging combination drugs and oral GLP-1RA formulations aimed at improving efficacy and patient adherence. In conclusion, the dorsomedial hypothalamus (DMH)\u2014a key GLP-1RA target\u2014mediates pre-ingestive cognitive satiation, while other hypothalamic GLP-1R neurons regulate diverse aspects of feeding behavior, offering potential therapeutic targets for obesity treatment.<\/jats:p>","DOI":"10.4093\/dmj.2025.0106","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T01:32:56Z","timestamp":1746149576000},"page":"333-347","update-policy":"https:\/\/doi.org\/10.4093\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Glucagon-Like Peptide-1 and Hypothalamic Regulation of Satiation: Cognitive and Neural Insights from Human and Animal Studies"],"prefix":"10.4093","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1901-8097","authenticated-orcid":true,"given":"Joon Seok","family":"Park","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu Sik","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0593-6978","authenticated-orcid":true,"given":"Hyung Jin","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2567","reference":[{"key":"ref1","first-page":"S70","volume-title":"Glucagon-like peptide 1 secretion by the L-cell: the view from within","author":"Lim","year":"2006"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.4159\/harvard.9780674366701.c111"},{"key":"ref3","first-page":"1076","volume-title":"Plasma insulin response to oral and intravenous glucose administration","author":"Elrick","year":"1964"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(64)90011-x"},{"key":"ref5","first-page":"826","volume-title":"Stimulation of insulin secretion by gastric inhibitory polypeptide in man","author":"Dupre","year":"1973"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.2.345"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.regpep.2004.09.001"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1038\/302716a0"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1172\/jci112855"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(87)81430-8"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(87)91194-9"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.15.2.270"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.08.088"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016\/s0021-9258(18)42531-8"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.004820"},{"key":"ref16","first-page":"513","volume-title":"Exendin-4 from Heloderma suspectum venom: from discovery to its latest application as type II diabetes combatant","author":"Yap","year":"2019"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1016\/s0021-9258(19)36565-2"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1042\/bj3120725"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(09)61375-1"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1411892"},{"key":"ref21","first-page":"e23780","volume-title":"Clinical effectiveness of liraglutide on weight loss in South Koreans: first real-world retrospective data on Saxenda in Asia","author":"Park","year":"2021"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2032183"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2307563"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.209"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007218"},{"key":"ref26","first-page":"27","volume-title":"A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents","author":"Finan","year":"2015"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2107519"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2206038"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/79.6.946"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1139\/apnm-2014-0549"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-789x.2010.00714.x"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1002\/ueg2.12097"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1016\/j.appet.2006.02.006"},{"key":"ref34","volume-title":""},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.3390\/nu13051391"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0802206"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1385\/jmn:18:1-2:07"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2019.0018"},{"key":"ref39","first-page":"863592","volume-title":"Brain activation in response to low-calorie food pictures: an explorative analysis of a randomized trial with dapagliflozin and exenatide","author":"van Ruiten","year":"2022"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac043"},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-1925"},{"key":"ref42","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-0772"},{"key":"ref43","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.09.010"},{"key":"ref44","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.026609"},{"key":"ref45","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201500167"},{"key":"ref46","doi-asserted-by":"publisher","DOI":"10.1038\/nature14416"},{"key":"ref47","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.01.033"},{"key":"ref48","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2024.07.017"},{"key":"ref49","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.11.036"},{"key":"ref50","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.06.014"},{"key":"ref51","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ado1820"},{"key":"ref52","doi-asserted-by":"publisher","DOI":"10.1002\/bies.202400016"},{"key":"ref53","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4392"},{"key":"ref54","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03729-3"},{"key":"ref55","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-1002"},{"key":"ref56","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2023.109637"},{"key":"ref57","doi-asserted-by":"publisher","DOI":"10.1172\/jci75276"},{"key":"ref58","doi-asserted-by":"publisher","DOI":"10.1124\/pr.115.011395"},{"key":"ref59","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.133429"},{"key":"ref60","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2015.00387"},{"key":"ref61","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2023.114108"},{"key":"ref62","first-page":"eabl7398","volume-title":"Integrative neurocircuits that control metabolism and food intake","author":"Bruning","year":"2023"},{"key":"ref63","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111698"},{"key":"ref64","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.06.002"},{"key":"ref65","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2015.07.008"},{"key":"ref66","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-020-02189-1"},{"key":"ref67","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1675"},{"key":"ref68","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2018.03.008"},{"key":"ref69","doi-asserted-by":"publisher","DOI":"10.1126\/science.adj2537"},{"key":"ref70","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abn5345"},{"key":"ref71","doi-asserted-by":"publisher","DOI":"10.2337\/db14-0302"},{"key":"ref72","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2023.103873"},{"key":"ref73","doi-asserted-by":"publisher","DOI":"10.1186\/s12986-021-00582-z"},{"key":"ref74","doi-asserted-by":"publisher","DOI":"10.1172\/jci157515"},{"key":"ref75","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adk4908"},{"key":"ref76","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08504-8"},{"key":"ref77","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2024.156100"},{"key":"ref78","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14309-w"},{"key":"ref79","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.06.031"},{"key":"ref80","doi-asserted-by":"publisher","DOI":"10.2337\/db16-1102"},{"key":"ref81","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1824"},{"key":"ref82","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2021.101352"},{"key":"ref83","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2019.07.008"},{"key":"ref84","doi-asserted-by":"publisher","DOI":"10.1159\/000512806"},{"key":"ref85","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.09.043"},{"key":"ref86","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-022-00914-3"},{"key":"ref87","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00854-0"},{"key":"ref88","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-024-01168-8"},{"key":"ref89","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.2032-23.2024"},{"key":"ref90","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-3291"},{"key":"ref91","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.1.101"},{"key":"ref92","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.02.028"},{"key":"ref93","doi-asserted-by":"publisher","DOI":"10.1172\/jci25483"},{"key":"ref94","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.09.042"},{"key":"ref95","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.10.016"},{"key":"ref96","doi-asserted-by":"publisher","DOI":"10.2337\/db17-1385"},{"key":"ref97","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2017.187"},{"key":"ref98","doi-asserted-by":"publisher","DOI":"10.1016\/0031-9384(71)90318-0"},{"key":"ref99","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00113.2017"},{"key":"ref100","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.11.010"},{"key":"ref101","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.991779"},{"key":"ref102","doi-asserted-by":"publisher","DOI":"10.2337\/dbi21-0003"},{"key":"ref103","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aay8071"},{"key":"ref104","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07685-6"},{"key":"ref105","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1096-9861(19990111)403:2<261::aid-cne8>3.0.co;2-5"},{"key":"ref106","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.86"},{"key":"ref107","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00460.2015"},{"key":"ref108","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2024.101960"},{"key":"ref109","doi-asserted-by":"publisher","DOI":"10.1172\/jci178239"},{"key":"ref110","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2015.47"},{"key":"ref111","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03412-w"},{"key":"ref112","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15677"},{"key":"ref113","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2024-086454"},{"key":"ref114","doi-asserted-by":"publisher","DOI":"10.1038\/s41366-024-01473-y"},{"key":"ref115","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07419-8"},{"key":"ref116","first-page":"8208","volume-title":"A small-molecule oral agonist of the human glucagon-like peptide-1 receptor","author":"Griffith","year":"2022"},{"key":"ref117","doi-asserted-by":"publisher","DOI":"10.1186\/s12902-024-01798-9"},{"key":"ref118","doi-asserted-by":"publisher","DOI":"10.2337\/db24-0463"},{"key":"ref119","first-page":"1553","volume-title":"Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension","author":"Wilding","year":"2022"},{"key":"ref120","first-page":"8056440","volume-title":"A comprehensive review on weight gain following discontinuation of glucagon-like peptide-1 receptor agonists for obesity","author":"Abdullah Bin Ahmed","year":"2024"}],"container-title":["Diabetes &amp; Metabolism Journal"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/e-dmj.org\/upload\/pdf\/dmj-2025-0106.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-dmj.org\/journal\/view.php?doi=10.4093\/dmj.2025.0106","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-dmj.org\/upload\/pdf\/dmj-2025-0106.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T02:17:10Z","timestamp":1747189030000},"score":1,"resource":{"primary":{"URL":"http:\/\/e-dmj.org\/journal\/view.php?doi=10.4093\/dmj.2025.0106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,1]]},"references-count":120,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,5]]}},"URL":"https:\/\/doi.org\/10.4093\/dmj.2025.0106","relation":{},"ISSN":["2233-6079","2233-6087"],"issn-type":[{"value":"2233-6079","type":"print"},{"value":"2233-6087","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,1]]},"assertion":[{"value":"2025-02-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-01","order":2,"name":"published","label":"Published online","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-01","order":3,"name":"published","label":"Print publication","group":{"name":"publication_history","label":"Publication History"}}]}}