{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:51:45Z","timestamp":1781657505915,"version":"3.54.5"},"reference-count":17,"publisher":"The Endocrine Society","issue":"7","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100013528","name":"Diabetes Canada","doi-asserted-by":"publisher","award":["OG-3-23-5790-RR"],"award-info":[{"award-number":["OG-3-23-5790-RR"]}],"id":[{"id":"10.13039\/100013528","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP 136938"],"award-info":[{"award-number":["MOP 136938"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020778","name":"University of Toronto Faculty of Medicine, BBDC and Heart & Stroke\/Richard Lewar Centre of Excellence in Cardiovascular Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020778","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Prolonged exposure to hormonal therapy can affect endogenous hormone secretion. In type 2 diabetes (T2DM), glucagon-like peptide-1 (GLP-1) receptor agonists are increasingly being administered in combination with therapies targeting additional hormones (including glucose-dependent insulinotropic polypeptide [GIP], glucagon, and insulin). However, little is known on how they affect endogenous GLP-1 secretion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We sought to evaluate the effect of exenatide b.i.d on endogenous secretion of GLP-1, GIP, and glucagon in patients treated concurrently with basal insulin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design\/Setting\/Patients<\/jats:title>\n                    <jats:p>In this trial, adults with T2DM were randomized to 8-week treatment with basal insulin glargine (Glar; n = 30), glargine plus thrice-daily lispro (Glar\/Lispro; n = 32), or glargine plus twice-daily exenatide (Glar\/Exe; n = 31).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Outcome<\/jats:title>\n                    <jats:p>Endogenous secretion of glucagon, GIP and GLP-1 was assessed on 2-hour oral glucose tolerance test (OGTT) at baseline and after stopping therapy at 8 weeks, during which their circulating concentrations were measured every 30 minutes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>There were no differences between groups in response profiles of glucagon and GIP. While there were no differences in fasting GLP-1, Glar\/Exe induced higher GLP-1 concentrations than the other treatments at 30 and 60 minutes post-challenge at 8 weeks (both P &amp;lt; .05). On the 8-week OGTT, baseline-adjusted GLP-1 was the highest in Glar\/Exe at each of 30 minutes (P = .037), 60 minutes (P = .007), and 90 minutes (P = .039). Unlike the respective between-group comparisons of baseline-adjusted area-under-the-curve (AUC) for glucagon and GIP (both P = NS), baseline-adjusted AUCGLP-1 at 8 weeks was the highest in Glar\/Exe (P = .037).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>When combined with basal insulin therapy, exenatide induces an enhanced post-challenge endogenous GLP-1 secretory response following its cessation, with no differential effect on glucagon and GIP secretion.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgag033","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T12:12:25Z","timestamp":1769515945000},"page":"e1884-e1891","source":"Crossref","is-referenced-by-count":0,"title":["Exenatide induces an enhanced endogenous glucagon-like peptide-1 secretory response in patients receiving basal insulin"],"prefix":"10.1210","volume":"111","author":[{"given":"Mihir","family":"Parikh","sequence":"first","affiliation":[{"name":"Department of Nutritional Sciences, Faculty of Medicine, University of Toronto , Toronto , Canada M5S 1A8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajie","family":"Pu","sequence":"additional","affiliation":[{"name":"Leadership Sinai Centre for Diabetes, Mount Sinai Hospital , Toronto , Canada M5T 3L9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwei","family":"Shen","sequence":"additional","affiliation":[{"name":"Leadership Sinai Centre for Diabetes, Mount Sinai Hospital , Toronto , Canada M5T 3L9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline K","family":"Kramer","sequence":"additional","affiliation":[{"name":"Leadership Sinai Centre for Diabetes, Mount Sinai Hospital , Toronto , Canada M5T 3L9"},{"name":"Division of Endocrinology, Department of Medicine, University of Toronto , Toronto , Canada M5S 1A8"},{"name":"Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital , Toronto , Canada M5G 1X5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Zinman","sequence":"additional","affiliation":[{"name":"Leadership Sinai Centre for Diabetes, Mount Sinai Hospital , Toronto , Canada M5T 3L9"},{"name":"Division of Endocrinology, Department of Medicine, University of Toronto , Toronto , Canada M5S 1A8"},{"name":"Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital , Toronto , Canada M5G 1X5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline L","family":"Beaudry","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Faculty of Medicine, University of Toronto , Toronto , Canada M5S 1A8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1989-027X","authenticated-orcid":false,"given":"Ravi","family":"Retnakaran","sequence":"additional","affiliation":[{"name":"Leadership Sinai Centre for Diabetes, Mount Sinai Hospital , Toronto , Canada M5T 3L9"},{"name":"Division of Endocrinology, Department of Medicine, University of Toronto , Toronto , Canada M5S 1A8"},{"name":"Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital , Toronto , Canada M5G 1X5"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"2026061619573010000_dgag033-B1","doi-asserted-by":"crossref","first-page":"105641","DOI":"10.1016\/j.psyneuen.2021.105641","article-title":"The neuroendocrinology of stress: glucocorticoid signaling mechanisms","volume":"137","author":"Herman","year":"2022","journal-title":"Psychoneuroendocrinology"},{"issue":"1-2","key":"2026061619573010000_dgag033-B2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mce.2006.03.042","article-title":"Functional neuroanatomy of thyroid hormone feedback in the human hypothalamus and pituitary gland","volume":"251","author":"Fliers","year":"2006","journal-title":"Mol Cell Endocrinol"},{"issue":"10","key":"2026061619573010000_dgag033-B3","doi-asserted-by":"crossref","first-page":"bqaf139","DOI":"10.1210\/endocr\/bqaf139","article-title":"Negative feedback loops and hormonal factors that regulate GH secretion","volume":"166","author":"de Sousa","year":"2025","journal-title":"Endocrinology"},{"issue":"1","key":"2026061619573010000_dgag033-B4","doi-asserted-by":"crossref","first-page":"e12724","DOI":"10.1111\/jne.12724","article-title":"Central aspects of systemic oestradiol negative- and positive-feedback on the reproductive neuroendocrine system","volume":"32","author":"Moenter","year":"2020","journal-title":"J Neuroendocrinol"},{"issue":"10","key":"2026061619573010000_dgag033-B5","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1007\/s00125-025-06499-z","article-title":"The role of the beta cell in type 2 diabetes: new findings from the last 5 years","volume":"68","author":"Yau","year":"2025","journal-title":"Diabetologia"},{"issue":"1","key":"2026061619573010000_dgag033-B6","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/S2213-8587(13)70006-8","article-title":"Short-term intensive insulin therapy in type 2 diabetes mellitus: a systematic review and meta-analysis","volume":"1","author":"Kramer","year":"2013","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"5","key":"2026061619573010000_dgag033-B7","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1210\/clinem\/dgad746","article-title":"Contemporary clinical perspectives on targeting remission of type 2 diabetes","volume":"109","author":"Retnakaran","year":"2024","journal-title":"J Clin Endocrinol Metab"},{"key":"2026061619573010000_dgag033-B8","doi-asserted-by":"crossref","first-page":"1293093","DOI":"10.3389\/fendo.2023.1293093","article-title":"Adolescents with obesity treated with exenatide maintain endogenous GLP-1, reduce DPP-4, and improve glycemic control","volume":"14","author":"Stenlid","year":"2023","journal-title":"Front Endocrinol"},{"issue":"2","key":"2026061619573010000_dgag033-B9","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1111\/dom.14242","article-title":"Effect of the glucagon-like peptide-1 analogue liraglutide versus placebo treatment on circulating proglucagon-derived peptides that mediate improvements in body weight, insulin secretion and action: a randomized controlled trial","volume":"23","author":"Kim","year":"2021","journal-title":"Diabetes Obes Metab"},{"issue":"5","key":"2026061619573010000_dgag033-B10","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1111\/dom.12858","article-title":"Chronic liraglutide therapy induces an enhanced endogenous glucagon-like peptide-1 secretory response in early type 2 diabetes","volume":"19","author":"Kramer","year":"2017","journal-title":"Diabetes Obes Metab"},{"issue":"1","key":"2026061619573010000_dgag033-B11","doi-asserted-by":"crossref","first-page":"6109","DOI":"10.1038\/s41467-022-33867-9","article-title":"The metabolic effects of adding exenatide to basal insulin therapy when targeting remission in early type 2 diabetes in a randomized clinical trial","volume":"13","author":"Retnakaran","year":"2022","journal-title":"Nat Commun"},{"issue":"1","key":"2026061619573010000_dgag033-B12","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s12933-023-01781-z","article-title":"The vascular function effects of adding exenatide or meal insulin to basal insulin therapy in early type 2 diabetes","volume":"22","author":"Retnakaran","year":"2023","journal-title":"Cardiovasc Diabetol"},{"issue":"14","key":"2026061619573010000_dgag033-B13","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1001\/jama.2025.14392","article-title":"New molecules and indications for GLP-1 medicines","volume":"334","author":"Gonzalez-Rellan","year":"2025","journal-title":"JAMA"},{"issue":"8","key":"2026061619573010000_dgag033-B14","first-page":"860","article-title":"Real-world persistence and adherence to glucagon-like peptide-1 receptor agonists among obese commercially insured adults without diabetes","volume":"30","author":"Gleason","year":"2024","journal-title":"J Manag Care Spec Pharm"},{"issue":"1","key":"2026061619573010000_dgag033-B15","doi-asserted-by":"crossref","first-page":"e2457349","DOI":"10.1001\/jamanetworkopen.2024.57349","article-title":"Discontinuation and reinitiation of dual-labeled GLP-1 receptor agonists among US adults with overweight or obesity","volume":"8","author":"Rodriguez","year":"2025","journal-title":"JAMA Netw Open"},{"issue":"6","key":"2026061619573010000_dgag033-B16","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1056\/NEJMoa2107519","article-title":"SURPASS-2 Investigators. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes","volume":"385","author":"Fr\u00edas","year":"2021","journal-title":"N Engl J Med"},{"issue":"6","key":"2026061619573010000_dgag033-B17","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1056\/NEJMoa2301972","article-title":"Retatrutide phase 2 obesity trial investigators. Triple-hormone-receptor agonist retatrutide for obesity\u2014a phase 2 trial","volume":"389","author":"Jastreboff","year":"2023","journal-title":"N Engl J Med"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgag033\/66613948\/dgag033.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/111\/7\/e1884\/66613948\/dgag033.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/111\/7\/e1884\/66613948\/dgag033.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T23:57:40Z","timestamp":1781654260000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/111\/7\/e1884\/8443512"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":17,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,1,28]]},"published-print":{"date-parts":[[2026,6,17]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgag033","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,7]]},"published":{"date-parts":[[2026,1,28]]}}}