{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T18:24:16Z","timestamp":1785781456487,"version":"3.56.0"},"reference-count":34,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"unspecified","delay-in-days":9,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Senior Research Fellowship 224485\/Z\/21\/Z"],"award-info":[{"award-number":["Senior Research Fellowship 224485\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UCL British Heart Foundation Accelerator","award":["AA\/18\/6\/34223"],"award-info":[{"award-number":["AA\/18\/6\/34223"]}]},{"DOI":"10.13039\/501100012317","name":"UCLH Biomedical Research Centre","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100012317","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MRC\/ NIHR Rare Disease Research UK Cardiovascular Initiative","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"crossref","award":["Future Leaders Fellowship MR\/X015017\/1"],"award-info":[{"award-number":["Future Leaders Fellowship MR\/X015017\/1"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["NIHR Doctoral Fellowship NIHR304689"],"award-info":[{"award-number":["NIHR Doctoral Fellowship NIHR304689"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open Diab Res Care"],"accepted":{"date-parts":[[2025,12,15]]},"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>There is growing interest in widening the use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) to all people with type 2 diabetes mellitus (T2DM). However, pivotal randomized controlled trials (RCTs) evaluated these drugs only in highly selected populations, often lacking generalizability to real-world populations. Understanding the effects of SGLT2i in populations where RCT evidence may be lacking is essential to help inform guideline development. To address this, we estimated the effect of empagliflozin in real-world users, many of whom would not have been eligible for the pivotal EMPA-REG RCT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We designed a trial emulation in UK primary care data, based on the EMPA-REG RCT, to assess the effect of empagliflozin in a more clinically relevant population. Adults with T2DM initiating empagliflozin (intervention) or dipeptidyl peptidase-4 inhibitors (active control) between January 1, 2014 and December 31, 2022 were included. Eligibility was extended to both RCT-eligible and RCT-ineligible individuals. The effect of empagliflozin on all-cause mortality was estimated using an adjusted Cox proportional hazards model, with stratified analyses by RCT eligibility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>The majority of people prescribed empagliflozin would not have met the EMPA-REG RCT eligibility criteria (11,011\/13,239, 83.2% RCT-ineligible). During follow-up, all-cause mortality occurred in 551 out of 13,239 (4.2%) in the empagliflozin group and 6,589 out of 49,264 (13.4%) in the active control group (adjusted HR 0.76, 95%\u2009CI 0.69 to 0.83). There was no evidence of differential treatment effect by RCT eligibility status (p-interaction=0.27).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Patients prescribed empagliflozin in real-world settings differ substantially from those enrolled in the EMPA-REG RCT. Using electronic health records, we demonstrate that the mortality benefit observed in EMPA-REG extends to a broader, more diverse real-world population, including those excluded from the original RCT. These findings provide a novel source of real-world evidence supporting the wider use of empagliflozin in routine clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjdrc-2025-005672","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T01:25:39Z","timestamp":1770686739000},"page":"e005672","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Enhancing evidence-based care using trial emulation in electronic health records: real-world effects of empagliflozin in people with type 2 diabetes"],"prefix":"10.1136","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1264-7165","authenticated-orcid":false,"given":"David K","family":"Ryan","sequence":"first","affiliation":[{"name":"Institute of Health Informatics, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth H","family":"Keogh","sequence":"additional","affiliation":[{"name":"Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6905-876X","authenticated-orcid":false,"given":"Elizabeth","family":"Williamson","sequence":"additional","affiliation":[{"name":"Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R Thomas","family":"Lumbers","sequence":"additional","affiliation":[{"name":"Institute of Health Informatics, UCL, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla","family":"Diaz-Ordaz","sequence":"additional","affiliation":[{"name":"Department of Statistical Science, University College London, London, England, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anoop D","family":"Shah","sequence":"additional","affiliation":[{"name":"Institute of Health Informatics, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7644-2030","authenticated-orcid":false,"given":"Patrick","family":"Bidulka","sequence":"additional","affiliation":[{"name":"Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"2026020917252854000_14.1.e005672.1","unstructured":"How many people in the UK have diabetes? diabetes UK. 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NICE Evidence Review 2022."},{"key":"2026020917252854000_14.1.e005672.3","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1093\/eurheartj\/ehz486","article-title":"ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: The Task Force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD)","volume":"41","author":"Cosentino","year":"2019","journal-title":"Eur Heart J"},{"key":"2026020917252854000_14.1.e005672.4","doi-asserted-by":"publisher","DOI":"10.2337\/dci18-0033"},{"key":"2026020917252854000_14.1.e005672.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"2026020917252854000_14.1.e005672.6","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.032038"},{"key":"2026020917252854000_14.1.e005672.7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1811744"},{"key":"2026020917252854000_14.1.e005672.8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812389"},{"key":"2026020917252854000_14.1.e005672.9","doi-asserted-by":"crossref","DOI":"10.1186\/s12933-023-02032-x","article-title":"Recent UK type 2 diabetes treatment guidance represents a near whole population indication for SGLT2-inhibitor therapy","volume":"22","author":"Young","year":"2023","journal-title":"Cardiovasc Diabetol"},{"key":"2026020917252854000_14.1.e005672.10","doi-asserted-by":"crossref","DOI":"10.1186\/s12874-022-01768-6","article-title":"Real-world data: a brief review of the methods, applications, challenges and opportunities","volume":"22","author":"Liu","year":"2022","journal-title":"BMC Med Res Methodol"},{"key":"2026020917252854000_14.1.e005672.11","unstructured":"Overview | nice real-world evidence framework | guidance | nice. 2022. 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