{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:35:26Z","timestamp":1792787726164,"version":"4.5.0"},"reference-count":25,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"European Union","award":["101095556"],"award-info":[{"award-number":["101095556"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100020655","name":"european health and digital executive agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020655","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UK Research and Innovation","id":[{"id":"https:\/\/ror.org\/001aqnf71","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Clinical Trials"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background\/Aims:<\/jats:title>\n                    <jats:p>The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results trial randomized patients with diabetes to liraglutide or placebo. The per-protocol analysis conditioned on post-baseline adherence and therefore lacked a well-defined estimand. This study sought to evaluate a subset of Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results to estimate the effect of sustained liraglutide exposure corresponding to a well-defined per-protocol analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method:<\/jats:title>\n                    <jats:p>We used the roadmap of targeting learning to define the estimand for the sustained treatment analysis and estimated it with longitudinal targeted minimum loss-based estimation, accounting for protocol deviations and censoring using post-baseline confounders. The results were compared to the intention-to-treat analysis. We report 3.5-year risks of the primary composite outcome (myocardial infarction, stroke, or cardiovascular mortality) and secondary outcomes (each of the primary outcome\u2019s components, revascularization, unstable angina pectoris, heart failure, and all-cause mortality).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>The intention-to-treat analysis estimated 3.5-year risks for the primary composite outcome of 11.8% (95% confidence interval: 10.8 to 12.8) in the liraglutide arm and 13.3% (95% confidence interval: 12.3 to 14.3) in the placebo arm, with a risk difference of 1.5% (95% confidence interval: 0.1 to 2.9). Accounting for post-baseline confounders, the sustained treatment analysis estimated 3.5-year risks of 11.4% (95% confidence interval: 10.4 to 12.5) for sustained exposure to liraglutide versus 12.6% (95% confidence interval: 11.5 to 13.7) for sustained exposure to placebo, yielding a risk difference of 1.1% (95% confidence interval: \u22120.4 to 2.6). Sustained exposure to liraglutide showed no statistically significant difference compared with sustained exposure to placebo for any secondary outcomes at 3.5\u2009years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>We used contemporary methods for causal inference to define and estimate the sustained treatment effects of the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results study by accounting for both baseline and time-varying confounders. The results were consistent with the findings of the original Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results trial.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17407745261449668","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:02:21Z","timestamp":1780390941000},"page":"517-525","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Accounting for non-adherence: A re-analysis of the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results trial"],"prefix":"10.1177","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9402-1317","authenticated-orcid":false,"given":"Kathrine Kold","family":"S\u00f8rensen","sequence":"first","affiliation":[{"name":"Copenhagen University Hospital, Steno Diabetes Center Copenhagen, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8794-6641","authenticated-orcid":false,"given":"Johan Sebastian","family":"Ohlendorff","sequence":"additional","affiliation":[{"name":"Copenhagen University Hospital, Steno Diabetes Center Copenhagen, Herlev, Denmark"},{"name":"Section of Biostatistics, Department of Public Health, University of Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Munch","sequence":"additional","affiliation":[{"name":"Section of Biostatistics, Department of Public Health, University of Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puriya Daniel W\u00fcrtz","family":"Yazdanfard","sequence":"additional","affiliation":[{"name":"Copenhagen University Hospital, Steno Diabetes Center Copenhagen, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6162-5205","authenticated-orcid":false,"given":"Mikkel Porsborg","family":"Andersen","sequence":"additional","affiliation":[{"name":"Copenhagen University Hospital, Steno Diabetes Center Copenhagen, Herlev, Denmark"},{"name":"The Prehospital Center, Region Zealand, N\u00e6stved, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0588-4880","authenticated-orcid":false,"given":"Ulrik","family":"Pedersen-Bjergaard","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nephrology, North Zealand University Hospital, Hiller\u00f8d, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bochra","family":"Zareini","sequence":"additional","affiliation":[{"name":"Copenhagen University Hospital, Steno Diabetes Center Copenhagen, Herlev, Denmark"},{"name":"Section of Biostatistics, Department of Public Health, University of Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5955-816X","authenticated-orcid":false,"given":"Thomas Alexander","family":"Gerds","sequence":"additional","affiliation":[{"name":"Section of Biostatistics, Department of Public Health, University of Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Torp-Pedersen","sequence":"additional","affiliation":[{"name":"Copenhagen University Hospital, Steno Diabetes Center Copenhagen, Herlev, Denmark"},{"name":"Section of Biostatistics, Department of Public Health, University of Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The REDDIE consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1603827"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2013.07.012"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4385"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.2825"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-65304-4"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1541-0420.2005.00377.x"},{"key":"e_1_3_3_8_2","doi-asserted-by":"crossref","unstructured":"van der Laan MJ Gruber S. 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