{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:15:31Z","timestamp":1791908131486,"version":"4.3.4"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T00:00:00Z","timestamp":1708128000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T00:00:00Z","timestamp":1708128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Clin Pharmacol"],"published-print":{"date-parts":[[2024,5]]},"DOI":"10.1007\/s00228-024-03646-0","type":"journal-article","created":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T12:02:13Z","timestamp":1708171333000},"page":"669-676","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["A review of an investigational drug retatrutide, a novel triple agonist agent for the treatment of obesity"],"prefix":"10.1007","volume":"80","author":[{"given":"Manmeet","family":"Kaur","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurav","family":"Misra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,17]]},"reference":[{"key":"3646_CR1","unstructured":"World health organization [Home page in Internet] Newsroom\/Fact sheets\/Detail\/Obesity and overweight. Available as: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/obesity-and-overweight. Last cited 6 Sept 2023"},{"key":"3646_CR2","volume-title":"Endotext [Internet]","author":"JQ Purnell","year":"2000","unstructured":"Purnell JQ (2000) Definitions, Classification, and Epidemiology of Obesity. In: Feingold KR, Anawalt B, Blackman MR et al (eds) Endotext [Internet]. MDText.com, Inc., South Dartmouth (MA).\u00a0https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK279167\/"},{"key":"3646_CR3","first-page":"1","volume":"14","author":"M Chaudharya","year":"2023","unstructured":"Chaudharya M, Sharma P (2023) Abdominal obesity in India: analysis of the National Family Health Survey-5 (2019\u20132021) data. Lancet 14:1\u201310","journal-title":"Lancet"},{"issue":"6","key":"3646_CR4","doi-asserted-by":"publisher","first-page":"802","DOI":"10.4093\/dmj.2020.0258","volume":"44","author":"JW Son","year":"2020","unstructured":"Son JW, Kim S (2020) Comprehensive review of current and upcoming anti-obesity drugs. Diabetes Metab J 44(6):802\u201318","journal-title":"Diabetes Metab J"},{"issue":"9","key":"3646_CR5","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1016\/j.cmet.2022.07.013","volume":"34","author":"T Coskun","year":"2022","unstructured":"Coskun T, Urva S, Roell WC, Qu H, Loghin C, Moyers JS et al (2022) LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: from discovery to clinical proof of concept. Cell Metab 34(9):1234-1247.e9","journal-title":"Cell Metab"},{"key":"3646_CR6","unstructured":"Drug.com [Home page in Internet] Retatrutide FDA Approval Status. Available as: https:\/\/www.drugs.com\/history\/retatrutide.html#:~:text=Last%20updated%20by%20Judith%20Stewart%2C%20BPharm%20on%20July%205%2C%202023.&text=Retatrutide%20is%20a%20gastric%20inhibitory,for%20the%20treatment%20of%20obesity. Last cited 6\u00a0Sept 2023"},{"issue":"9","key":"3646_CR7","doi-asserted-by":"publisher","first-page":"2784","DOI":"10.1111\/dom.15167","volume":"25","author":"S Urva","year":"2023","unstructured":"Urva S, O\u2019Farrell L, Du Y, Loh MT, Hemmingway A, Qu H, Alsina-Fernandez J, Haupt A, Milicevic Z, Coskun T (2023) The novel GIP, GLP-1 and glucagon receptor agonist retatrutide delays gastric emptying. Diabetes Obes Metab 25(9):2784\u20132788","journal-title":"Diabetes Obes Metab"},{"issue":"8","key":"3646_CR8","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1007\/s12630-023-02550-y","volume":"70","author":"PM Jones","year":"2023","unstructured":"Jones PM, Hobai IA, Murphy PM (2023) Anesthesia and glucagon-like peptide-1 receptor agonists: proceed with caution! Can J Anaesth 70(8):1281\u20131286","journal-title":"Can J Anaesth"},{"issue":"18","key":"3646_CR9","doi-asserted-by":"publisher","first-page":"8621","DOI":"10.1016\/S0021-9258(18)68350-4","volume":"263","author":"T Buhl","year":"1988","unstructured":"Buhl T, Thim L, Kofod H, Orskov C, Harling H, Holst JJ (1988) Naturally occurring products of proglucagon 111\u2013160 in the porcine and human small intestine. J Biol Chem 263(18):8621\u20138624","journal-title":"J Biol Chem"},{"issue":"9","key":"3646_CR10","doi-asserted-by":"publisher","first-page":"2757","DOI":"10.2337\/diabetes.51.9.2757","volume":"51","author":"F Reimann","year":"2002","unstructured":"Reimann F, Gribble FM (2002) Glucose-sensing in glucagon-like peptide-1-secreting cells. Diabetes 51(9):2757\u20132763","journal-title":"Diabetes"},{"key":"3646_CR11","doi-asserted-by":"publisher","first-page":"2131","DOI":"10.1053\/j.gastro.2007.03.054","volume":"132","author":"LL Baggio","year":"2007","unstructured":"Baggio LL, Drucker DJ (2007) Biology of incretins: GLP-1 and GIP. Gastroenterology 132:2131\u20132157","journal-title":"Gastroenterology"},{"key":"3646_CR12","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1016\/j.pharmthera.2006.11.007","volume":"113","author":"ME Doyle","year":"2007","unstructured":"Doyle ME, Egan JM (2007) Mechanisms of action of glucagon-like peptide 1 in the pancreas. Pharmacol Ther 113:546\u2013593","journal-title":"Pharmacol Ther"},{"issue":"3","key":"3646_CR13","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1002\/dmrr.2608","volume":"31","author":"RC Moffett","year":"2015","unstructured":"Moffett RC, Patterson S, Irwin N, Flatt PR (2015) Positive effects of GLP-1 receptor activation with liraglutide on pancreatic islet morphology and metabolic control in C57BL\/KsJ db\/db mice with degenerative diabetes. Diabetes Metab Res Rev 31(3):248\u2013255","journal-title":"Diabetes Metab Res Rev"},{"issue":"6","key":"3646_CR14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0101005","volume":"9","author":"S Vasu","year":"2014","unstructured":"Vasu S, Moffett RC, Thorens B, Flatt PR (2014) Role of endogenous GLP-1 and GIP in beta cell compensatory responses to insulin resistance and cellular stress. PLoS ONE 9(6):e101005","journal-title":"PLoS ONE"},{"issue":"6","key":"3646_CR15","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/j.cmet.2010.04.007","volume":"11","author":"YZ De Marinis","year":"2010","unstructured":"De Marinis YZ, Salehi A, Ward CE, Zhang Q, Abdulkader F, Bengtsson M et al (2010) GLP-1 inhibits and adrenaline stimulates glucagon release by differential modulation of N- and L-type Ca2+ channel-dependent exocytosis. Cell Metab 11(6):543\u2013553","journal-title":"Cell Metab"},{"issue":"11","key":"3646_CR16","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.122.029282","volume":"12","author":"ED Michos","year":"2023","unstructured":"Michos ED, Lopez-Jimenez F, Gulati M (2023) Role of glucagon-like peptide-1 receptor agonists in achieving weight loss and improving cardiovascular outcomes in people with overweight and obesity. J Am Heart Assoc 12(11):e029282","journal-title":"J Am Heart Assoc"},{"issue":"12","key":"3646_CR17","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1111\/j.1365-2826.2012.02364.x","volume":"24","author":"MA Labouesse","year":"2012","unstructured":"Labouesse MA, Stadlbauer U, Weber E, Arnold M, Langhans W, Pacheco-L\u00f3pez G (2012) Vagal afferents mediate early satiation and prevent flavour avoidance learning in response to intraperitoneally infused exendin-4. J Neuroendocrinol 24(12):1505\u20131516","journal-title":"J Neuroendocrinol"},{"key":"3646_CR18","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.molmet.2019.09.010","volume":"30","author":"TD M\u00fcller","year":"2019","unstructured":"M\u00fcller TD, Finan B, Bloom SR, D\u2019Alessio D, Drucker DJ, Flatt PR et al (2019) Glucagon-like peptide 1 (GLP-1). Mol Metab 30:72\u2013130","journal-title":"Mol Metab"},{"issue":"3","key":"3646_CR19","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1111\/dom.14280","volume":"23","author":"M Friedrichsen","year":"2021","unstructured":"Friedrichsen M, Breitschaft A, Tadayon S, Wizert A, Skovgaard D (2021) The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity. Diabetes Obes Metab 23(3):754\u2013762","journal-title":"Diabetes Obes Metab"},{"issue":"Suppl 2","key":"3646_CR20","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1111\/j.1463-1326.2012.01579.x","volume":"14","author":"T Vilsb\u00f8ll","year":"2012","unstructured":"Vilsb\u00f8ll T, Garber AJ (2012) Non-glycaemic effects mediated via GLP-1 receptor agonists and the potential for exploiting these for therapeutic benefit: focus on liraglutide. Diabetes Obes Metab 14(Suppl 2):41\u201349","journal-title":"Diabetes Obes Metab"},{"issue":"6","key":"3646_CR21","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.133429","volume":"5","author":"S Gabery","year":"2020","unstructured":"Gabery S, Salinas CG, Paulsen SJ et al (2020) Semaglutide lowers body weight in rodents via distributed neural pathways. JCI Insight 5(6):e133429","journal-title":"JCI Insight"},{"issue":"4","key":"3646_CR22","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1016\/j.cmet.2018.03.001","volume":"27","author":"DJ Drucker","year":"2018","unstructured":"Drucker DJ (2018) Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab 27(4):740\u2013756","journal-title":"Cell Metab"},{"issue":"1","key":"3646_CR23","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/BF00492251","volume":"56","author":"AM Buchan","year":"1978","unstructured":"Buchan AM, Polak JM, Capella C, Solcia E, Pearse AG (1978) Electronimmunocytochemical evidence for the K cell localization of gastric inhibitory polypeptide (GIP) in man. Histochemistry 56(1):37\u201344","journal-title":"Histochemistry"},{"issue":"1","key":"3646_CR24","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/S0305-0491(98)10110-4","volume":"121","author":"TP Mommsen","year":"1998","unstructured":"Mommsen TP, Mojsov S (1998) Glucagon-like peptide-1 activates the adenylyl cyclase system in rockfish enterocytes and brain membranes. Comp Biochem Physiol B Biochem Mol Biol 121(1):49\u201356","journal-title":"Comp Biochem Physiol B Biochem Mol Biol"},{"key":"3646_CR25","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1111\/j.1432-1033.1993.tb17986.x","volume":"214","author":"R Mentlein","year":"1993","unstructured":"Mentlein R, Gallwitz B, Schmidt WE (1993) Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide- 1(7\u201336)amide, peptide histidine methionine and is responsible for their degradation in human serum. Eur J Biochem 214:829\u2013835","journal-title":"Eur J Biochem"},{"key":"3646_CR26","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1111\/j.2040-1124.2010.00022.x","volume":"1","author":"Y Seino","year":"2010","unstructured":"Seino Y, Fukushima M, Yabe D (2010) GIP and GLP-1, the two incretin hormones: similarities and differences. J Diabetes Investig 1:8\u201323","journal-title":"J Diabetes Investig"},{"issue":"6","key":"3646_CR27","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/j.tem.2020.02.006","volume":"31","author":"RJ Samms","year":"2020","unstructured":"Samms RJ, Coghlan MP, Sloop KW (2020) How may gip enhance the therapeutic efficacy of GLP-1? Trends Endocrinol Metab 31(6):410\u2013421","journal-title":"Trends Endocrinol Metab"},{"key":"3646_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2020.101139","volume":"46","author":"JE Campbell","year":"2021","unstructured":"Campbell JE (2021) Targeting the GIPR for obesity: To agonize or antagonize? Potential mechanisms Mol Metab 46:101139","journal-title":"Potential mechanisms Mol Metab"},{"issue":"2","key":"3646_CR29","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1530\/JOE-19-0201","volume":"243","author":"JH Stern","year":"2019","unstructured":"Stern JH, Smith GI, Chen S, Unger RH, Klein S, Scherer PE (2019) Obesity dysregulates fasting-induced changes in glucagon secretion. J Endocrinol 243(2):149\u2013160","journal-title":"J Endocrinol"},{"issue":"17","key":"3646_CR30","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.140532","volume":"5","author":"FS Willard","year":"2020","unstructured":"Willard FS, Douros JD, Gabe MB, Showalter AD, Wainscott DB, Suter TM et al (2020) Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist. JCI Insight 5(17):e140532","journal-title":"JCI Insight"},{"issue":"472","key":"3646_CR31","doi-asserted-by":"publisher","first-page":"eaat3392","DOI":"10.1126\/scitranslmed.aat3392","volume":"10","author":"EA Killion","year":"2018","unstructured":"Killion EA, Wang J, Yie J, Shi SD, Bates D, Min X et al (2018) Anti-obesity effects of GIPR antagonists alone and in combination with GLP-1R agonists in preclinical models. Sci Transl Med 10(472):eaat3392","journal-title":"Sci Transl Med"},{"issue":"3","key":"3646_CR32","doi-asserted-by":"publisher","first-page":"819","DOI":"10.2337\/db14-1052","volume":"64","author":"LS Jun","year":"2015","unstructured":"Jun LS, Millican RL, Hawkins ED, Konkol DL, Showalter AD, Christe ME, Michael MD, Sloop KW (2015) Absence of glucagon and insulin action reveals a role for the GLP-1 receptor in endogenous glucose production. Diabetes 64(3):819\u2013827","journal-title":"Diabetes"},{"key":"3646_CR33","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.molmet.2018.09.009","volume":"18","author":"T Coskun","year":"2018","unstructured":"Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB et al (2018) LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: from discovery to clinical proof of concept. Mol Metab 18:3\u201314","journal-title":"Mol Metab"},{"issue":"2","key":"3646_CR34","doi-asserted-by":"publisher","first-page":"235","DOI":"10.2337\/db16-0994","volume":"66","author":"JJ Holst","year":"2017","unstructured":"Holst JJ, Wewer Albrechtsen NJ, Pedersen J, Knop FK (2017) Glucagon and amino acids are linked in a mutual feedback cycle: the liver-\u03b1-cell axis. Diabetes 66(2):235\u2013240","journal-title":"Diabetes"},{"issue":"9","key":"3646_CR35","doi-asserted-by":"publisher","first-page":"bvab118","DOI":"10.1210\/jendso\/bvab118","volume":"5","author":"RB Vega","year":"2021","unstructured":"Vega RB, Whytock KL, Gassenhuber J, Goebel B, Tillner J, Agueusop I et al (2021) A metabolomic signature of glucagon action in healthy individuals with overweight\/obesity. J Endocr Soc 5(9):bvab118","journal-title":"J Endocr Soc"},{"issue":"5","key":"3646_CR36","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1080\/13543784.2023.2206560","volume":"32","author":"SA Doggrell","year":"2023","unstructured":"Doggrell SA (2023) Is retatrutide (LY3437943), a GLP-1, GIP, and glucagon receptor agonist, a step forward in the treatment of diabetes and obesity? Expert Opin Investig Drugs 32(5):355\u2013359","journal-title":"Expert Opin Investig Drugs"},{"issue":"10366","key":"3646_CR37","doi-asserted-by":"publisher","first-page":"1869","DOI":"10.1016\/S0140-6736(22)02033-5","volume":"400","author":"S Urva","year":"2022","unstructured":"Urva S, Coskun T, Loh MT, Du Y, Thomas MK, Gurbuz S et al (2022) LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Lancet 400(10366):1869\u20131881","journal-title":"Lancet"},{"issue":"6","key":"3646_CR38","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1056\/NEJMoa2301972","volume":"389","author":"AM Jastreboff","year":"2023","unstructured":"Jastreboff AM, Kaplan LM, Fr\u00edas JP, Wu Q, Du Y, Gurbuz S et al (2023) Retatrutide phase 2 obesity trial investigators. triple-hormone-receptor agonist retatrutide for obesity - a phase 2 trial. N Engl J Med 389(6):514\u2013526","journal-title":"N Engl J Med"},{"issue":"10401","key":"3646_CR39","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/S0140-6736(23)01053-X","volume":"402","author":"J Rosenstock","year":"2023","unstructured":"Rosenstock J, Frias J, Jastreboff AM, Du Y, Lou J, Gurbuz S et al (2023) Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. Lancet 402(10401):529\u2013544","journal-title":"Lancet"},{"key":"3646_CR40","unstructured":"Clinical trial.gov [Home page in Internet] A study of retatrutide (LY3437943) in participants with obesity and cardiovascular disease (TRIUMPH-3). Available as: https:\/\/classic.clinicaltrials.gov\/ct2\/show\/record\/NCT05882045. Last cited 8\u00a0Sept 2023"}],"container-title":["European Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00228-024-03646-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00228-024-03646-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00228-024-03646-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T06:11:11Z","timestamp":1712556671000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00228-024-03646-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,17]]},"references-count":40,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["3646"],"URL":"https:\/\/doi.org\/10.1007\/s00228-024-03646-0","relation":{},"ISSN":["0031-6970","1432-1041"],"issn-type":[{"value":"0031-6970","type":"print"},{"value":"1432-1041","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,17]]},"assertion":[{"value":"8 September 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 February 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 February 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Since it is a review article, they are not required.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Yes.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"None of the authors have competing interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Since it is a review article, this is not required.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human ethics committee"}}]}}