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This study compared real-world weight reduction and cardiometabolic parameters associated with tirzepatide and semaglutide for obesity management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective cohort study was conducted using Truveta de-identified US electronic health record data. Adults with obesity or overweight and \u2265\u20091 obesity-related complication, without diabetes, who initiated tirzepatide or semaglutide December 2023\u2013June 2024 and adhered to treatment, were followed for 6 months. Primary outcome was percentage weight change from baseline. Secondary outcomes included weight-reduction targets and changes in body mass index (BMI) and cardiometabolic parameters. Primary analysis employed propensity-score weighted regression. Sensitivity analyses included modified intention-to-treat.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 2,396 on-treatment patients (1,003 tirzepatide; 1,393 semaglutide), greater 6-month mean percentage weight reduction was observed with tirzepatide (\u201311.15% vs. \u22128.83%; adjusted difference \u22122.32%-points [95% CI: \u22123.17, \u22121.48]). Higher proportions of tirzepatide-treated patients achieved 5%, 10%, 15%, and 20% weight-reduction targets. Greater reductions in BMI, blood pressure, and haemoglobin A1c were observed with tirzepatide. More patients received higher doses of semaglutide (\u2265\u20091.7\u00a0mg; 67.7%) vs. tirzepatide (\u2265\u200910\u00a0mg; 42.4%). Sensitivity analysis findings were consistent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Consistent with clinical trials, real-world tirzepatide treatment was associated with greater 6-month weight reduction and more frequent achievement of weight-reduction targets and improvements in select cardiometabolic parameters than semaglutide among adults with obesity without diabetes. This early emergence of tirzepatide\u2019s comparative advantage over semaglutide was observed despite more semaglutide-treated patients receiving higher doses than tirzepatide-treated patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s40618-025-02792-1","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T10:46:15Z","timestamp":1770633975000},"page":"413-423","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Comparative effectiveness of tirzepatide and semaglutide for obesity management in US clinical practice: a 6-month retrospective cohort study"],"prefix":"10.1007","volume":"49","author":[{"given":"Carel W.","family":"le Roux","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolae","family":"Done","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4303-2515","authenticated-orcid":false,"given":"Alan J. 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AZ was, at the time of the study, an employee of Analysis Group, Inc., a consulting firm that received funding for this research from Eli Lilly and Company. GKD, AB, IL, JD, and ZK are employees of Eli Lilly and Company and hold stock or stock options in Eli Lilly and Company. HK was an employee of Eli Lilly and Company at the time of the study. CWR reports payments to the institution from the Irish Research Council, Health Research Board, Science Foundation Ireland, and Anabio; consulting fees from NovoNordisk, Eli Lilly, Johnson&Johnson, Boehringer Ingelheim, GI Dynamics, Herbalife, Altimmune, Irish Life Health, Amgen, Arrowhead, Roche, AstraZeneca, Keyron, Gila Pharmaceuticals, Metsera, Nymble, AbbVie, and Olympus; payments for presentations from NovoNordisk, Herbalife, Johnson&Johnson, Eli Lilly, Boehringer Ingelheim, Rhythm Pharmaceuticals, and Currax Pharmaceuticals; support for attending meetings and\/or travel from NovoNordisk, Herbalife, Johnson&Johnson, Eli Lilly, and Boehringer Ingelheim; stock\/stock options as payment for scientific advisory board contributions from Metsera and Nymble; an unpaid leadership\/fiduciary role in the Irish Society for Nutrition and Metabolism; and is a co-owner providing clinical obesity care for My Best Weight and Beyond BMI.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The data that support the findings of this study were licensed from Truveta. Per the Data Use Agreement between Lilly and Truveta, the deposition of data into publicly available repositories is not allowed.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data sharing"}},{"value":"The study is considered exempt research by the United States Department of Health and Human Services under 45 CFR \u00a7\u00a046.104(d)(4) as it involved only the secondary use of data that were de-identified in compliance with the Health Insurance Portability and Accountability Act (HIPAA), specifically, 45 CFR \u00a7\u00a0164.514.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics statement"}}]}}