{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T04:22:17Z","timestamp":1794198137541,"version":"4.8.0"},"reference-count":48,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Incretin\u2010based therapies have transformed the management of obesity and type 2 diabetes (T2D). Pivotal randomized controlled trials (RCTs) report substantial weight loss and glycemic improvements; the extent to which these translate to clinical populations remains uncertain. Seven 2026\u2010published RCT meta\u2010analyses (comprising 127 RCTs and 58\u2009976 participants) were compared with 26 real\u2010world studies identified through structured PubMed search. Primary outcomes were body weight loss and HbA1c reduction; secondary outcomes included major adverse cardiovascular events (MACE), neurological end\u2010points, and safety. The comparison is descriptive. For T2D, real\u2010world semaglutide achieved 4.7\u201310.5\u2009kg weight loss (6\u201312\u2009months) and 1.0\u20131.3 percentage\u2010point HbA1c reductions, lower than RCT meta\u2010analytic estimates (tirzepatide mean difference [MD] \u22129.55% vs. placebo). Without diabetes, real\u2010world persister analyses (SHAPE study: semaglutide \u221214.1%, tirzepatide \u221216.5%) approximated per\u2010protocol RCT estimates (semaglutide \u221214.9%, tirzepatide 15\u2009mg \u221220.9%), whereas intention\u2010to\u2010treat real\u2010world estimates were substantially lower. Just 13% of semaglutide users reached 2.4\u2009mg and 25.9% of tirzepatide users reached 15\u2009mg. Real\u2010world cardiovascular data showed 20%\u201346% MACE reductions, broadly consistent with the RCT reduction. Differences between T2D and non\u2010T2D populations likely reflect channeling bias and differential follow\u2010up. Real\u2010world incretin\u2010based therapy effectiveness is broadly consistent with RCT efficacy when dose attainment is accounted for. High discontinuation rates (20%\u201350% within 1\u2009year) and prior GLP\u20101 RA exposure track with the observed efficacy gap. Clinicians can expect RCT\u2010level outcomes in patients who tolerate and persist with target doses. Head\u2010to\u2010head cardiovascular outcome trials comparing tirzepatide and semaglutide in non\u2010diabetic populations are needed.<\/jats:p>","DOI":"10.1111\/1753-0407.70248","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T10:15:57Z","timestamp":1783505757000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Real\u2010World vs. Randomized Trial Evidence for Incretin\u2010Based Therapies: A Narrative Review"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3863-9267","authenticated-orcid":false,"given":"Zachary","family":"Bloomgarden","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes and Bone Disease Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(25)00355\u20101"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20108587(25)00299\u20102"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2032183"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2206038"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2107519"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2307563"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc24\u20101082"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.16364"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2025.8222"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.100947"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.70698"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.70169"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325\u2010026\u201003523\u20105"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.70676"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2026.1758755"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2010.07.015"},{"key":"e_1_2_9_18_1","unstructured":"D. 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