{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:39:15Z","timestamp":1792467555756,"version":"4.5.0"},"reference-count":26,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"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"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Little is known about how glucagon\u2010like peptide\u20101 receptor agonists (GLP\u20101RA) are initiated in real\u2010world settings and whether prescribing behaviours in routine care contribute to the high discontinuation rates seen in practice. We examined prescribing behaviours for injectable semaglutide at treatment initiation and evaluated their impact on early medication discontinuation and on 1\u2010year persistence among US adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Using MarketScan data (2018\u20132021), this retrospective cohort study identified US adults with diabetes and\/or obesity on no prior incretin therapy starting injectable semaglutide. Initiating dose was categorized as low or high (\u2264\u20090.5 and \u2265\u20091.0\u2009mg\/week, respectively); treatment status was followed for 12\u2009months. Medication persistence was estimated using Kaplan\u2013Meier analysis. Piecewise Cox proportional hazards regression assessed early discontinuation risk, logistic regression assessed the odds of high\u2010dose initiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among this cohort of 48\u2009658 adults, 14.5% were started on semaglutide using high doses. The off\u2010label high\u2010dose regimen was associated with decreased 1\u2010year persistence (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01), and a 25% increase in early discontinuation risk (HR: 1.25, 95% CI: 1.17\u20131.34,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) independently of age, obesity status, co\u2010morbidity measures and cost. Odds of high\u2010dose initiation were increased in the West and South (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), for endocrinologists (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02), for patients who were male (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), younger (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02), with obesity versus overweight (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002), and for treatment initiation in 2018 compared with 2019\u20132021 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Initiation of injectable semaglutide therapy using high doses is common in real\u2010world settings. High\u2010dose initiation represents a modifiable risk factor for early medication discontinuation and decreased 1\u2010year persistence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71448","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:55:11Z","timestamp":1792464911000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Real\u2010World Semaglutide Initiation Behaviours in the United States: Impact on Early Treatment Discontinuation and on 1\u2010Year Persistence"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1052-6658","authenticated-orcid":false,"given":"L. Maria","family":"Belalcazar","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine University of Texas Medical Branch  Galveston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daoqi","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Data Sciences University of Texas Medical Branch  Galveston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saman","family":"Modi","sequence":"additional","affiliation":[{"name":"Division of General Medicine, Department of Internal Medicine University of Texas Medical Branch  Galveston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aima","family":"Meer","sequence":"additional","affiliation":[{"name":"John Sealy School of Medicine University of Texas Medical Branch  Galveston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong\u2010Fang","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Data Sciences University of Texas Medical Branch  Galveston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,19]]},"reference":[{"issue":"1","key":"e_1_2_8_2_1","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2024.57349","article-title":"Discontinuation and Reinitiation of Dual\u2010Labeled GLP\u20101 Receptor Agonists Among US Adults With Overweight or Obesity","volume":"8","author":"Rodriguez P. J.","year":"2025","journal-title":"JAMA Network Open"},{"issue":"5","key":"e_1_2_8_3_1","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2024.13172","article-title":"GLP\u20101 Receptor Agonist Discontinuation Among Patients With Obesity and\/or Type 2 Diabetes","volume":"7","author":"Do D.","year":"2024","journal-title":"JAMA Network Open"},{"issue":"7","key":"e_1_2_8_4_1","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1002\/oby.24315","article-title":"Titration and Discontinuation of Semaglutide for Weight Management in Commercially Insured US Adults","volume":"33","author":"Xu Y.","year":"2025","journal-title":"Obesity (Silver Spring)"},{"issue":"5","key":"e_1_2_8_5_1","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.pcd.2024.06.013","article-title":"Adherence and Persistence Among People With Type 2 Diabetes Newly Initiating Oral Semaglutide Versus DPP\u20104is in a US Real\u2010World Setting","volume":"18","author":"Lv L.","year":"2024","journal-title":"Primary Care Diabetes"},{"issue":"11","key":"e_1_2_8_6_1","doi-asserted-by":"crossref","first-page":"5239","DOI":"10.1111\/dom.15872","article-title":"Adherence to Glucagon\u2010Like Peptide\u20101 Receptor Agonist Treatment in Type 2 Diabetes Mellitus: A Nationwide Registry Study","volume":"26","author":"Lassen M. C. H.","year":"2024","journal-title":"Diabetes, Obesity and Metabolism"},{"issue":"8","key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.2337\/dc24-2746","article-title":"Association of Patient Cost Sharing With Adherence to GLP\u20101RA and Adverse Health Outcomes","volume":"48","author":"Zhang D.","year":"2025","journal-title":"Diabetes Care"},{"issue":"2","key":"e_1_2_8_8_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.2337\/dc15-0165","article-title":"A Phase 2, Randomized, Dose\u2010Finding Study of the Novel Once\u2010Weekly Human GLP\u20101 Analog, Semaglutide, Compared With Placebo and Open\u2010Label Liraglutide in Patients With Type 2 Diabetes","volume":"39","author":"Nauck M. A.","year":"2016","journal-title":"Diabetes Care"},{"issue":"11","key":"e_1_2_8_9_1","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.2337\/dci24-0003","article-title":"Efficacy and Safety of GLP\u20101 Medicines for Type 2 Diabetes and Obesity","volume":"47","author":"Drucker D. J.","year":"2024","journal-title":"Diabetes Care"},{"issue":"10","key":"e_1_2_8_10_1","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1001\/jamacardio.2020.1966","article-title":"Use of Glucagon\u2010Like Peptide\u20101 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease: A Review","volume":"5","author":"Honigberg M. C.","year":"2020","journal-title":"JAMA Cardiology"},{"issue":"1","key":"e_1_2_8_11_1","doi-asserted-by":"crossref","DOI":"10.3390\/jcm12010145","article-title":"Clinical Recommendations to Manage Gastrointestinal Adverse Events in Patients Treated With Glp\u20101 Receptor Agonists: A Multidisciplinary Expert Consensus","volume":"12","author":"Gorgojo\u2010Martinez J. J.","year":"2022","journal-title":"Journal of Clinical Medicine"},{"issue":"19","key":"e_1_2_8_12_1","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1056\/NEJMoa1607141","article-title":"Semaglutide and Cardiovascular Outcomes in Patients With Type 2 Diabetes","volume":"375","author":"Marso S. P.","year":"2016","journal-title":"New England Journal of Medicine"},{"issue":"24","key":"e_1_2_8_13_1","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1056\/NEJMoa2307563","article-title":"Semaglutide and Cardiovascular Outcomes in Obesity Without Diabetes","volume":"389","author":"Lincoff A. M.","year":"2023","journal-title":"New England Journal of Medicine"},{"issue":"3","key":"e_1_2_8_14_1","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1080\/00949655.2017.1397151","article-title":"Statistical Power to Detect Violation of the Proportional Hazards Assumption When Using the Cox Regression Model","volume":"88","author":"Austin P. C.","year":"2018","journal-title":"Journal of Statistical Computation and Simulation"},{"issue":"4","key":"e_1_2_8_15_1","doi-asserted-by":"crossref","first-page":"3386","DOI":"10.1111\/dom.70535","article-title":"Real\u2010World Persistence and Dose Titration of GLP\u20101 Receptor Agonists in Type 2 Diabetes: A UK Population\u2010Based Cohort Study by Obesity and Cardiovascular Disease Status","volume":"28","author":"Ulrich F. S.","year":"2026","journal-title":"Diabetes, Obesity and Metabolism"},{"issue":"1","key":"e_1_2_8_16_1","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/dom.14195","article-title":"Adherence and Persistence Among Patients With Type 2 Diabetes Initiating Dulaglutide Compared With Semaglutide and Exenatide BCise: 6\u2010Month Follow\u2010Up From US Real\u2010World Data","volume":"23","author":"Mody R.","year":"2021","journal-title":"Diabetes, Obesity and Metabolism"},{"issue":"9","key":"e_1_2_8_17_1","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.2337\/dc25-0690","article-title":"Gradual Titration of Semaglutide Results in Better Treatment Adherence and Fewer Adverse Events: A Randomized Controlled Open\u2010Label Pilot Study Examining a 16\u2010Week Flexible Titration Regimen Versus Label\u2010Recommended 8\u2010Week Semaglutide Titration Regimen","volume":"48","author":"Eldor R.","year":"2025","journal-title":"Diabetes Care"},{"issue":"2","key":"e_1_2_8_18_1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1001\/jama.2024.22284","article-title":"Discontinuation of Glucagon\u2010Like Peptide\u20101 Receptor Agonists","volume":"333","author":"Khan S. 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B.","year":"2000","journal-title":"International Journal of Technology Assessment in Health Care"},{"issue":"2","key":"e_1_2_8_26_1","doi-asserted-by":"crossref","DOI":"10.1093\/ofid\/ofac584","article-title":"Regional Variation in Outpatient Antibiotic Prescribing for Acute Respiratory Tract Infections in a Commercially Insured Population, United States, 2017","volume":"10","author":"Bizune D.","year":"2023","journal-title":"Open Forum Infectious Diseases"},{"issue":"4","key":"e_1_2_8_27_1","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1055\/a-2085-2299","article-title":"High Prescribing and State\u2010Level Variation in Z\u2010Drug Use Among Medicare Patients","volume":"56","author":"Anderson K. E.","year":"2023","journal-title":"Pharmacopsychiatry"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.71448","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dom.71448","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.71448","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:55:15Z","timestamp":1792464915000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/10.1111\/dom.71448"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,19]]},"references-count":26,"alternative-id":["10.1111\/dom.71448"],"URL":"https:\/\/doi.org\/10.1111\/dom.71448","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,19]]},"assertion":[{"value":"2026-06-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"dom.71448"}}