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This study aimed to evaluate the cardiovascular and kidney outcomes of\n GLP<\/jats:styled-content>\n \u2010\n 1RAs<\/jats:styled-content>\n versus other anti\u2010obesity medications (\n AOMs<\/jats:styled-content>\n ) in adults with obesity.\n <\/jats:p>\n <\/jats:sec>\n \n Materials and Methods<\/jats:title>\n \n This target trial emulation used\n TriNetX<\/jats:styled-content>\n electronic health records (July 2021\u2013May 2025) to identify adults with obesity and no diabetes history who initiated\n GLP<\/jats:styled-content>\n \u2010\n 1RAs<\/jats:styled-content>\n (liraglutide, semaglutide, or tirzepatide) or other\n AOMs<\/jats:styled-content>\n . Outcomes included major adverse cardiovascular events (\n MACE<\/jats:styled-content>\n ), major adverse kidney events (\n MAKE<\/jats:styled-content>\n ), all\u2010cause mortality, mental health conditions, and safety outcomes. Propensity score matching (1:1) balanced baseline characteristics; Cox models estimated hazard ratios (\n HRs<\/jats:styled-content>\n ) with 95% confidence intervals (\n CIs<\/jats:styled-content>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The study included 140\u2009169 matched pairs of\n GLP<\/jats:styled-content>\n \u2010\n 1RA<\/jats:styled-content>\n and\n AOM<\/jats:styled-content>\n initiators. Mean follow\u2010up was 392\u2009days for\n GLP<\/jats:styled-content>\n \u2010\n 1RA<\/jats:styled-content>\n users and 564\u2009days for\n AOM<\/jats:styled-content>\n users. Compared to\n AOMs<\/jats:styled-content>\n ,\n GLP<\/jats:styled-content>\n \u2010\n 1RA<\/jats:styled-content>\n use was associated with lower risks of\n MACE<\/jats:styled-content>\n (\n HR<\/jats:styled-content>\n , 0.76; 95%\n CI<\/jats:styled-content>\n , 0.72\u20130.81),\n MAKE<\/jats:styled-content>\n (\n HR<\/jats:styled-content>\n , 0.64; 95%\n CI<\/jats:styled-content>\n , 0.55\u20130.74), and all\u2010cause mortality (\n HR<\/jats:styled-content>\n , 0.49; 95%\n CI<\/jats:styled-content>\n , 0.42\u20130.57). Mental health outcomes also improved, with reduced risks of depression (\n HR<\/jats:styled-content>\n , 0.63), suicidal ideation\/attempt (\n HR<\/jats:styled-content>\n , 0.42), and substance use disorder (\n HR<\/jats:styled-content>\n , 0.58).\n GLP<\/jats:styled-content>\n \u2010\n 1RAs<\/jats:styled-content>\n were not associated with increased risks of acute pancreatitis (\n HR<\/jats:styled-content>\n , 1.17), hypoglycemia (\n HR<\/jats:styled-content>\n , 1.08), or gastrointestinal symptoms (\n HR<\/jats:styled-content>\n , 0.99).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Among adults with obesity but without diabetes,\n GLP<\/jats:styled-content>\n \u2010\n 1RA<\/jats:styled-content>\n use was associated with reduced cardiovascular, kidney, mortality, and mental health risks compared to other\n AOMs<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/dom.70054","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T09:51:33Z","timestamp":1756374693000},"page":"6527-6536","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Cardiovascular and kidney outcomes of\n GLP<\/scp>\n \u20101 receptor agonists in adults with obesity: A target trial emulation study"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5814-6657","authenticated-orcid":false,"given":"Huilin","family":"Tang","sequence":"first","affiliation":[{"name":"The Center for Health AI and Synthesis of Evidence (CHASE) University of Pennsylvania Philadelphia Pennsylvania USA"},{"name":"Department of Biostatistics, Epidemiology, and Informatics University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Lu","sequence":"additional","affiliation":[{"name":"The Center for Health AI and Synthesis of Evidence (CHASE) University of Pennsylvania Philadelphia Pennsylvania USA"},{"name":"The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Center for Health AI and Synthesis of Evidence (CHASE) University of Pennsylvania Philadelphia Pennsylvania USA"},{"name":"The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhou","sequence":"additional","affiliation":[{"name":"The Center for Health AI and Synthesis of Evidence (CHASE) University of Pennsylvania Philadelphia Pennsylvania USA"},{"name":"Department of Biostatistics, Epidemiology, and Informatics University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dazheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Center for Health AI and Synthesis of Evidence (CHASE) University of Pennsylvania Philadelphia Pennsylvania USA"},{"name":"Department of Biostatistics, Epidemiology, and Informatics University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajie","family":"Chen","sequence":"additional","affiliation":[{"name":"The Center for Health AI and Synthesis of Evidence (CHASE) University of Pennsylvania Philadelphia Pennsylvania USA"},{"name":"Department of Biostatistics, Epidemiology, and Informatics University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Chen","sequence":"additional","affiliation":[{"name":"Pfizer Inc. 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