{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:58:31Z","timestamp":1791496711456,"version":"4.3.4"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T00:00:00Z","timestamp":1681171200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To describe the design of the SOUL trial (Semaglutide cardiOvascular oUtcomes triaL) and the baseline clinical data of its participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      In SOUL, the effects of oral semaglutide, the first oral glucagon\u2010like peptide\u20101 receptor agonist, on the risk of cardiovascular (CV) events in individuals with type 2 diabetes and established atherosclerotic CV disease (ASCVD) and\/or chronic kidney disease (CKD) will be assessed. SOUL is a randomized, double\u2010blind, parallel\u2010group, placebo\u2010controlled CV outcomes trial comparing oral semaglutide (14\u2009mg once daily) with placebo, both in addition to standard of care, in individuals aged \u226550\u2009years with type 2 diabetes and evidence of ASCVD (coronary artery disease [CAD], cerebrovascular disease, symptomatic peripheral arterial disease [PAD]) and\/or CKD (estimated glomerular filtration rate\u2009&lt;60\u2009mL\/min\/1.73\u2009m\n                      <jats:sup>2<\/jats:sup>\n                      ). The primary outcome is time from randomization to first occurrence of a major adverse CV event (MACE; a composite of CV death, nonfatal myocardial infarction or nonfatal stroke). This event\u2010driven trial will continue until 1225 first adjudication\u2010confirmed MACEs have occurred. Enrolment has been completed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall, 9650 participants were enrolled between June 17, 2019 and March 24, 2021 (men 71.1%, White ethnicity 68.9%, mean age 66.1\u2009years, diabetes duration 15.4\u2009years, body mass index 31.1\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      , glycated haemoglobin 63.5\u2009mmol\/mol [8.0%]). The most frequently used antihyperglycaemic medications at baseline were metformin (75.7%), insulin and insulin analogues (50.5%), sulphonylureas (29.1%), sodium\u2010glucose cotransporter\u20102 inhibitors (26.7%) and dipeptidyl peptidase\u20104 inhibitors (23.0%). At randomization, 70.7% of participants had CAD, 42.3% had CKD, 21.1% had cerebrovascular disease and 15.7% had symptomatic PAD (categories not mutually exclusive). Prevalent heart failure was reported in 23.0% of participants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SOUL will provide evidence regarding the CV effects of oral semaglutide in individuals with type 2 diabetes and established ASCVD and\/or CKD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.15058","type":"journal-article","created":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T01:56:21Z","timestamp":1679450181000},"page":"1932-1941","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":121,"title":["Effects of oral semaglutide on cardiovascular outcomes in individuals with type 2 diabetes and established atherosclerotic cardiovascular disease and\/or chronic kidney disease: Design and baseline characteristics of\n                    <scp>SOUL<\/scp>\n                    , a randomized trial"],"prefix":"10.1111","volume":"25","author":[{"given":"Darren K.","family":"McGuire","sequence":"first","affiliation":[{"name":"University of Texas Southwestern Medical Center, and Parkland Health and Hospital System  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodica P.","family":"Busui","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Metabolism, Endocrinology and Diabetes University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Deanfield","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences, University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1254-6636","authenticated-orcid":false,"given":"Silvio E.","family":"Inzucchi","sequence":"additional","affiliation":[{"name":"Section of Endocrinology, Yale School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3154-5332","authenticated-orcid":false,"given":"Johannes F. E.","family":"Mann","sequence":"additional","affiliation":[{"name":"KfH Kidney Center  Munich Germany"},{"name":"Friedrich Alexander University of Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaus","family":"Marx","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I University Hospital Aachen, RWTH Aachen University  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon L.","family":"Mulvagh","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology Dalhousie University  Halifax Nova Scotia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Poulter","sequence":"additional","affiliation":[{"name":"Imperial Clinical Trials Unit, Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mads D. M.","family":"Engelmann","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S  S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Kees","family":"Hovingh","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S  S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Sejersten","family":"Ripa","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S  S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette","family":"Gislum","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S  S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1752-2054","authenticated-orcid":false,"given":"Kirstine","family":"Brown\u2010Frandsen","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S  S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John B.","family":"Buse","sequence":"additional","affiliation":[{"name":"University of North Carolina School of Medicine  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/dci22-0034"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1800256"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc22-S010"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/1479164109353367"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(21)00203-5"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2020.4511"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14054"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2018.12.001"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1607141"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1901118"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.033502"},{"key":"e_1_2_9_13_1","unstructured":"Novo Nordisk A\/S. SAXENDA\u00ae Highlights of Prescribing Information.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/206321s015lbl.pdf. Accessed September 27 2022"},{"key":"e_1_2_9_14_1","unstructured":"Eli Lilly and company.TRULICITY\u00ae Highlights of Prescribing Information.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/125469s033lbl.pdf. Accessed September 27 2022"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc22-S002"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-150-9-200905050-00006"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2021.08.003"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.01112"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118645"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2005.53221.x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/gps.5033"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/gps.5085"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31149-3"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2108269"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32261-X"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1612917"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509225"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1603827"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01584-3"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01499-w"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.645507"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.042155"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1811744"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812389"},{"key":"e_1_2_9_35_1","unstructured":"ClinicalTrials.gov.A Research Study to Look at how Semaglutide Compared to Placebo Affects Diabetic Eye Disease in People with Type 2 Diabetes (FOCUS).https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03811561. Accessed 1 February 2023"},{"key":"e_1_2_9_36_1","unstructured":"ClinicalTrials.gov.Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT).https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03574597?term=NCT03574597&draw=2&rank=1. Accessed 17 February 2023"},{"key":"e_1_2_9_37_1","unstructured":"ClinicalTrials.gov.A Research Study to See how Semaglutide Works Compared to Placebo in People with Type 2 Diabetes and Chronic Kidney Disease (FLOW).https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03819153?term=NCT03819153&draw=2&rank=1. Accessed 17 February 2023"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13553"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13028"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz486"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc22-S009"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.15058","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.15058","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T04:25:17Z","timestamp":1761884717000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.15058"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,11]]},"references-count":40,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1111\/dom.15058"],"URL":"https:\/\/doi.org\/10.1111\/dom.15058","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/DOM.15058\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15058\/v2\/review4","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15058\/v2\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15058\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15058\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15058\/v1\/review7","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15058\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15058\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15058\/v1\/review4","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15058\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15058\/v1\/review6","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15058\/v1\/review5","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15058\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15058\/v1\/review1","asserted-by":"object"}]},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,11]]},"assertion":[{"value":"2023-01-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}