{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:08:05Z","timestamp":1792512485161,"version":"4.5.0"},"reference-count":30,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004337","name":"Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Metabolism"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1016\/j.molmet.2025.102291","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T07:52:24Z","timestamp":1764316344000},"page":"102291","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":8,"special_numbering":"C","title":["Effects of CT-388, a once-weekly signaling-biased dual GLP-1\/GIP receptor agonist, on weight loss and glycemic control in preclinical models and participants with obesity"],"prefix":"10.1016","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3699-150X","authenticated-orcid":false,"given":"Manu V.","family":"Chakravarthy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Hergarden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Elliott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan P.","family":"Frias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico A.","family":"Arg\u00fcelles-Tello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Tenorio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan E.","family":"Rankin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingtao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyam","family":"Krishnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Erlanson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond V.","family":"Fucini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Bone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey S.","family":"Iwig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Acosta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Untereiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmita","family":"Pant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avalon","family":"Patton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leyla L.","family":"Sanchez-Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Steinberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damian","family":"Bialonczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stig K.","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.molmet.2025.102291_bib1","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1056\/NEJMra1514009","article-title":"Mechanisms, pathophysiology, and management of obesity","volume":"376","author":"Heymsfield","year":"2017","journal-title":"N Engl J Med"},{"key":"10.1016\/j.molmet.2025.102291_bib2","doi-asserted-by":"crossref","first-page":"S102","DOI":"10.1161\/01.cir.0000437739.71477.ee","article-title":"2013 AHA\/ACC\/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology\/American Heart Association Task Force on Practice Guidelines and the Obesity Society","volume":"129","author":"Jensen","year":"2014","journal-title":"Circulation"},{"key":"10.1016\/j.molmet.2025.102291_bib3","series-title":"World Obesity Atlas 2024","year":"2024"},{"key":"10.1016\/j.molmet.2025.102291_bib4","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/S0140-6736(23)02750-2","article-title":"Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults","volume":"403","year":"2024","journal-title":"Lancet"},{"key":"10.1016\/j.molmet.2025.102291_bib5","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/S0140-6736(21)00213-0","article-title":"Semaglutide 2\u00b74 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial","volume":"397","author":"Davies","year":"2021","journal-title":"Lancet"},{"key":"10.1016\/j.molmet.2025.102291_bib6","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1056\/NEJMoa2206038","article-title":"Tirzepatide once weekly for the treatment of obesity","volume":"387","author":"Jastreboff","year":"2022","journal-title":"N Engl J Med"},{"key":"10.1016\/j.molmet.2025.102291_bib7","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1056\/NEJMoa2306963","article-title":"Semaglutide in patients with heart failure with preserved ejection fraction and obesity","volume":"389","author":"Kosiborod","year":"2023","journal-title":"N Engl J Med"},{"key":"10.1016\/j.molmet.2025.102291_bib8","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0140-6736(21)01324-6","article-title":"Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial","volume":"398","author":"Rosenstock","year":"2021","journal-title":"Lancet"},{"key":"10.1016\/j.molmet.2025.102291_bib9","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1056\/NEJMoa2032183","article-title":"Once-weekly semaglutide in adults with overweight or obesity","volume":"384","author":"Wilding","year":"2021","journal-title":"N Engl J Med"},{"key":"10.1016\/j.molmet.2025.102291_bib10","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1056\/NEJMoa2301972","article-title":"Triple-hormone-receptor agonist retatrutide for obesity \u2013 a phase 2 trial","volume":"389","author":"Jastreboff","year":"2023","journal-title":"N Engl J Med"},{"key":"10.1016\/j.molmet.2025.102291_bib11","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S0140-6736(23)01053-X","article-title":"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","volume":"402","author":"Rosenstock","year":"2023","journal-title":"Lancet"},{"key":"10.1016\/j.molmet.2025.102291_bib12","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nrd.2017.229","article-title":"Biased signalling: from simple switches to allosteric microprocessors","volume":"17","author":"Smith","year":"2018","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.molmet.2025.102291_bib13","doi-asserted-by":"crossref","DOI":"10.1016\/j.molmet.2023.101762","article-title":"Discovery of ecnoglutide \u2013 a novel, long-acting, cAMP-biased glucagon-like peptide-1 (GLP-1) analog","volume":"75","author":"Guo","year":"2023","journal-title":"Mol Metabol"},{"key":"10.1016\/j.molmet.2025.102291_bib14","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/dom.15288","article-title":"Abolishing \u03b2-arrestin recruitment is necessary for the full metabolic benefits of G protein-biased glucagon-like peptide-1 receptor agonists","volume":"26","author":"Hinds","year":"2024","journal-title":"Diabetes Obes Metabol"},{"key":"10.1016\/j.molmet.2025.102291_bib15","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1038\/s41467-018-03941-2","article-title":"Targeting GLP-1 receptor trafficking to improve agonist efficacy","volume":"9","author":"Jones","year":"2018","journal-title":"Nat Commun"},{"key":"10.1016\/j.molmet.2025.102291_bib16","doi-asserted-by":"crossref","DOI":"10.1016\/j.molmet.2020.100991","article-title":"Disconnect between signalling potency and in vivo efficacy of pharmacokinetically optimised biased glucagon-like peptide-1 receptor agonists","volume":"37","author":"Lucey","year":"2020","journal-title":"Mol Metabol"},{"key":"10.1016\/j.molmet.2025.102291_bib17","doi-asserted-by":"crossref","first-page":"3905","DOI":"10.1111\/bph.15134","article-title":"Signalling, trafficking and glucoregulatory properties of glucagon-like peptide-1 receptor agonists exendin-4 and lixisenatide","volume":"177","author":"Pickford","year":"2020","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.molmet.2025.102291_bib18","article-title":"Biased agonism of GLP-1R and GIPR enhances glucose lowering and weight loss, with dual GLP-1R\/GIPR biased agonism yielding greater efficacy","volume":"6","author":"Rodriguez","year":"2025","journal-title":"Cell Rep Med"},{"issue":"Suppl 1","key":"10.1016\/j.molmet.2025.102291_bib19","doi-asserted-by":"crossref","first-page":"742","DOI":"10.2337\/db24-742-P","article-title":"A phase 3 evaluation of cAMP signaling biased GLP-1 analog ecnoglutide (XW003) in adults with type 2 diabetes","volume":"73","author":"Zhu","year":"2024","journal-title":"Diabetes"},{"key":"10.1016\/j.molmet.2025.102291_bib20","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.140532","article-title":"Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist","volume":"5","author":"Willard","year":"2020","journal-title":"JCI Insight"},{"key":"10.1016\/j.molmet.2025.102291_bib21","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1056\/NEJMoa2107519","article-title":"Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes","volume":"385","author":"Fr\u00edas","year":"2021","journal-title":"N Engl J Med"},{"key":"10.1016\/j.molmet.2025.102291_bib22","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1001\/jamainternmed.2024.2525","article-title":"Semaglutide vs tirzepatide for weight loss in adults with overweight or obesity","volume":"184","author":"Rodriguez","year":"2024","journal-title":"JAMA Intern Med"},{"key":"10.1016\/j.molmet.2025.102291_bib23","series-title":"Inventors; Sunesis Pharmaceuticals, Inc, assignee. Methods of chemotype evolution. US patent 10,107,798 B2","author":"Hansen","year":"2018"},{"key":"10.1016\/j.molmet.2025.102291_bib24","doi-asserted-by":"crossref","first-page":"10","DOI":"10.2337\/cd22-as01","article-title":"Standards of Medical Care in Diabetes-2022 abridged for primary care providers","volume":"40","year":"2022","journal-title":"Clin Diabetes"},{"key":"10.1016\/j.molmet.2025.102291_bib25","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.molmet.2018.09.009","article-title":"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","volume":"18","author":"Coskun","year":"2018","journal-title":"Mol Metabol"},{"key":"10.1016\/j.molmet.2025.102291_bib26","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1111\/bph.15497","article-title":"The therapeutic potential of GLP-1 receptor biased agonism","volume":"179","author":"Jones","year":"2022","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.molmet.2025.102291_bib27","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.bcp.2018.01.040","article-title":"Human GIP(3-30)NH(2) inhibits G protein-dependent as well as G protein-independent signaling and is selective for the GIP receptor with high-affinity binding to primate but not rodent GIP receptors","volume":"150","author":"Gabe","year":"2018","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.molmet.2025.102291_bib28","doi-asserted-by":"crossref","DOI":"10.1016\/j.molmet.2021.101181","article-title":"Spatiotemporal GLP-1 and GIP receptor signaling and trafficking\/recycling dynamics induced by selected receptor mono- and dual-agonists","volume":"49","author":"Novikoff","year":"2021","journal-title":"Mol Metabol"},{"key":"10.1016\/j.molmet.2025.102291_bib29","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1038\/ijo.2013.162","article-title":"Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults","volume":"38","author":"van Can","year":"2014","journal-title":"Int J Obes"},{"issue":"Supplement 1","key":"10.1016\/j.molmet.2025.102291_bib30","doi-asserted-by":"crossref","first-page":"i31","DOI":"10.1093\/jcag\/gwae059.081","article-title":"Gastrointestinal events associated with glucagon-like peptide-1 (GLP-1) agonists in overweight patients: a systematic review and meta-analysis","volume":"8","author":"Verma","year":"2025","journal-title":"J Can Assoc Gastroenterol"}],"container-title":["Molecular Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S221287782500198X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S221287782500198X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T10:18:50Z","timestamp":1768472330000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S221287782500198X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":30,"alternative-id":["S221287782500198X"],"URL":"https:\/\/doi.org\/10.1016\/j.molmet.2025.102291","relation":{},"ISSN":["2212-8778"],"issn-type":[{"value":"2212-8778","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Effects of CT-388, a once-weekly signaling-biased dual GLP-1\/GIP receptor agonist, on weight loss and glycemic control in preclinical models and participants with obesity","name":"articletitle","label":"Article Title"},{"value":"Molecular Metabolism","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.molmet.2025.102291","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Genentech. Published by Elsevier GmbH.","name":"copyright","label":"Copyright"}],"article-number":"102291"}}