{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T08:05:04Z","timestamp":1789632304687,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"abstract":"ABSTRACT<\/jats:title>\n \n Objective<\/jats:title>\n To assess change in long\u2010term predicted 10\u2010year cardiometabolic risk (Type 2 diabetes [T2D] and cardiovascular disease [CVD]) in adults with overweight or obesity without T2D.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This post hoc analysis used data from ATTAIN\u20101, a Phase 3 trial in adults (\u2265\u200918\u2009years) with obesity (BMI \u2265\u200930\u2009kg\/m\n 2<\/jats:sup>\n ) or overweight (BMI \u2265\u200927\u2009kg\/m\n 2<\/jats:sup>\n with \u2265\u20091 obesity\u2010related complication) without T2D. Participants received orforglipron 5.5\u2009mg, 9\u2009mg, or 17.2\u2009mg, or placebo for 72\u2009weeks. Changes in predicted risk from baseline to 72\u2009weeks were assessed using three validated risk prediction engines: Cardiometabolic Disease Staging (T2D risk), Framingham (total CVD risk), and PREVENT (total CVD, ASCVD, and HF risk). Mixed models for repeated measures compared change from baseline risk scores between groups.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n At week 72, mean relative reduction from baseline (median baseline scores: 16.0%\u201317.3%) in T2D risk score was significantly greater with orforglipron than placebo (\u221248.6% to \u221259.4% vs. \u221210.5%;\n p<\/jats:italic>\n \u2009<\u20090.0001; HR\u2010range 0.43\u20130.55). Using Framingham, at week 72, orforglipron was associated with a significant decrease in mean absolute change in total CVD risk vs placebo (\u22120.6% to \u22121.00% vs. +0.6%;\n p<\/jats:italic>\n \u2009<\u20090.0001; HR range: 0.82\u20130.87). Similarly, at week 72, orforglipron was associated with reduced predicted ASCVD, HF, and total CVD risks compared to placebo, assessed using PREVENT (\n p<\/jats:italic>\n \u2009<\u20090.0001).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n In this post hoc analysis, once\u2010daily oral orforglipron was associated with statistically significant improvements in predicted 10\u2010year risk of incident T2D and CVD compared with placebo over 72\u2009weeks using three validated risk prediction models.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ATTAIN\u20101:\n NCT05869903<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/dom.71322","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T07:31:23Z","timestamp":1789630283000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Predicting the Long\u2010Term Risk of Type 2 Diabetes and Cardiovascular Disease With Orforglipron in People With Overweight or Obesity: A Post Hoc Analysis of the\n ATTAIN<\/scp>\n \u20101 Trial"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0120-7580","authenticated-orcid":false,"given":"Shraddha","family":"Shinde","sequence":"first","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Kahles","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care Medicine University Hospital RWTH Aachen Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Vasileva\u2010Metodiev","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Griffin","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9534-0483","authenticated-orcid":false,"given":"Hong","family":"Liu\u2010Seifert","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremie","family":"Lebrec","sequence":"additional","affiliation":[{"name":"HaaPACS GmbH Schriesheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neena A.","family":"Xavier","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runjia","family":"Li","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne R.","family":"Klise","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambrish","family":"Singh","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Aberle","sequence":"additional","affiliation":[{"name":"University Medical Center Hamburg\u2010Eppendorf Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"issue":"6","key":"e_1_2_13_2_1","doi-asserted-by":"crossref","DOI":"10.1002\/osp4.70094","article-title":"The Identification of Potential Treatment Targets to Reduce the Risk of Obesity\u2010Related Complications: A Step Toward a Treat\u2010To\u2010Target Approach in Obesity Management","volume":"11","author":"Busetto L.","year":"2025","journal-title":"Obesity Science and Practice"},{"key":"e_1_2_13_3_1","unstructured":"WHO \u201cIssues Global Guideline on the Use of GLP\u20101 Medicines in Treating Obesity \u201d(2026)."},{"issue":"3","key":"e_1_2_13_4_1","article-title":"Obesity: Clinical Impact, Pathophysiology, Complications, and Modern Innovations in Therapeutic Strategies","volume":"12","author":"Ullah M. 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