{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T17:52:58Z","timestamp":1794073978769,"version":"4.8.0"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>There is growing evidence that the GLP\u20101 system is implicated in alcohol and other substance use disorders, and that GLP\u20101\u2010based therapies may have therapeutic relevance in alcohol use disorder (AUD). We aimed to determine the impact of GLP\u20101 based therapies on incident AUDs in a real\u2010world setting in patients with T2D.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and Methods<\/jats:title>\n                    <jats:p>We conducted emulation target trials based on a real\u2010world network of electronic health records (EHRs) from over 120 million patients in the United States of America. Four target trials were emulated among eligible patients with type 2 diabetes (T2D) who had no prior AUD diagnosis by comparing tirzepatide, semaglutide, liraglutide, and dulaglutide with DPP4 inhibitors (DPP4i). First\u2010ever diagnosis of AUD occurred within an 18\u2010month follow\u2010up period and was examined using Kaplan\u2013Meier survival analyses. Four target trial cohorts were generated and compared with a reference arm of patients treated with DPP4i: cohort (1) treatment with tirzepatide; cohort (2) treatment with semaglutide; cohort (3) treatment with liraglutide; and cohort (4) treatment with dulaglutide. Cohorts underwent propensity score matching 1:1 for confounders. We examined rates of incident AUD (ICD\u201010 code F10) and performed head\u2010to\u2010head analyses of the incretin\u2010based therapies. We also performed sensitivity analyses relating to whether treatment was adjunctive therapy with metformin and by treatment adherence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After propensity\u2010score matching, we identified four target trials of patients treated with tirzepatide (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20097165), semaglutide (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200920\u2009198), liraglutide (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096565), and dulaglutide (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200919\u2009061); 1:1 with the reference (DPP4i) patients. Tirzepatide and semaglutide (but not liraglutide or dulaglutide) were associated with significant risk reduction of incident AUD compared to DPP4i (hazard ratio 0.47 [95% confidence interval 0.29, 0.75] and 0.68 [0.52, 0.89], respectively). Head\u2010to\u2010head comparison revealed tirzepatide had a significant risk reduction compared to liraglutide in incident AUD (0.47 [0.24, 0.92]).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In patients with T2D, tirzepatide and semaglutide treatment is associated with a lower incidence of AUD; robust randomised, controlled evidence for the use of these drugs for this novel indication is appropriate.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70169","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T06:55:01Z","timestamp":1759906501000},"page":"137-150","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Relative efficacy of\n                    <scp>GLP<\/scp>\n                    \u20101 and\n                    <scp>GLP<\/scp>\n                    \u20101\/\n                    <scp>GIP<\/scp>\n                    receptor agonists in the prevention of alcohol\u2010use disorders using a target trial emulation approach"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8066-9470","authenticated-orcid":false,"given":"Alex E.","family":"Henney","sequence":"first","affiliation":[{"name":"Department of Cardiovascular &amp; Metabolic Medicine University of Liverpool  Liverpool UK"},{"name":"Metabolism &amp; Nutrition Research Group Liverpool University Hospitals NHS Foundation Trust  Merseyside Liverpool UK"},{"name":"Liverpool Centre for Cardiovascular Sciences University of Liverpool and Liverpool University Hospitals NHS Foundation Trust  Merseyside Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Riley","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular &amp; Metabolic Medicine University of Liverpool  Liverpool UK"},{"name":"Metabolism &amp; Nutrition Research Group Liverpool University Hospitals NHS Foundation Trust  Merseyside Liverpool UK"},{"name":"Liverpool Centre for Cardiovascular Sciences University of Liverpool and Liverpool University Hospitals NHS Foundation Trust  Merseyside Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Heague","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular &amp; Metabolic Medicine University of Liverpool  Liverpool UK"},{"name":"Metabolism &amp; Nutrition Research Group Liverpool University Hospitals NHS Foundation Trust  Merseyside Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl A.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Psychology, Institute of Population Health University of Liverpool  Merseyside UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa J.","family":"Hydes","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular &amp; Metabolic Medicine University of Liverpool  Liverpool UK"},{"name":"Metabolism &amp; Nutrition Research Group Liverpool University Hospitals NHS Foundation Trust  Merseyside Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Anson","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular &amp; Metabolic Medicine University of Liverpool  Liverpool UK"},{"name":"Metabolism &amp; Nutrition Research Group Liverpool University Hospitals NHS Foundation Trust  Merseyside Liverpool UK"},{"name":"Liverpool Centre for Cardiovascular Sciences University of Liverpool and Liverpool University Hospitals NHS Foundation Trust  Merseyside Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Deparment of Health Data Science, Institute of Population Health University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uazman","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular &amp; Metabolic Medicine University of Liverpool  Liverpool UK"},{"name":"Metabolism &amp; Nutrition Research Group Liverpool University Hospitals NHS Foundation Trust  Merseyside Liverpool UK"},{"name":"Liverpool Centre for Cardiovascular Sciences University of Liverpool and Liverpool University Hospitals NHS Foundation Trust  Merseyside Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Cuthbertson","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular &amp; Metabolic Medicine University of Liverpool  Liverpool UK"},{"name":"Metabolism &amp; Nutrition Research Group Liverpool University Hospitals NHS Foundation Trust  Merseyside Liverpool UK"},{"name":"Liverpool Centre for Cardiovascular Sciences University of Liverpool and Liverpool University Hospitals NHS Foundation Trust  Merseyside Liverpool 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