{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T03:10:25Z","timestamp":1793848225943,"version":"4.6.1"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"23","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Novo Nordisk A\/S","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2025,6,10]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Both GLP-1 (glucagon-like peptide-1) receptor agonists and SGLT2 (sodium-glucose cotransporter-2) inhibitors (SGLT2i) improve cardiovascular outcomes in people with type 2 diabetes and cardiovascular or chronic kidney disease. However, there are limited data about the effect of combining these agents on cardiovascular and safety outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>The SOUL trial (Semaglutide Cardiovascular Outcomes Trial; NCT03914326) randomized 9650 participants with type 2 diabetes and atherosclerotic cardiovascular disease and\/or chronic kidney disease to oral semaglutide or placebo. As prespecified, participants were analyzed according to baseline use of SGLT2i (yes, n=2596; no, n=7054), and subsequently for any use of SGLT2i during the trial (yes, n=4718; no, n=4932). The primary outcome was time to first major adverse cardiovascular event, defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Safety was evaluated by comparing the incidence of serious adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Over a mean follow-up of 47.5\u00b110.9 months, the risk of the primary outcome in the overall trial population was 14% lower for oral semaglutide versus placebo (hazard ratio, 0.86; 95% CI, 0.77\u20130.96). In those taking SGLT2i at baseline, there were 143 of 1296 (semaglutide) versus 158 of 1300 (placebo) primary outcome events (hazard ratio, 0.89; 95% CI, 0.71\u20131.11); and 436 of 3529 versus 510 of 3525, respectively, in participants not taking SGLT2i at baseline (hazard ratio, 0.84; 95% CI, 0.74\u20130.95;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      -interaction, 0.66). An analysis of major adverse cardiovascular events by any in-trial SGLT2i use versus no use also showed no evidence of heterogeneity in the effects of oral semaglutide. The adverse event profiles of oral semaglutide with or without concomitant SGLT2i were similar.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Oral semaglutide reduced major adverse cardiovascular event outcomes independently of concomitant SGLT2i treatment, and this combination appeared to be safe.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>REGISTRATION:<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT03914326.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.125.074545","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T14:30:25Z","timestamp":1743258625000},"page":"1639-1650","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":79,"title":["Oral Semaglutide and Cardiovascular Outcomes in People With Type 2 Diabetes, According to SGLT2i Use: Prespecified Analyses of the SOUL Randomized Trial"],"prefix":"10.1161","volume":"151","clinical-trial-number":[{"clinical-trial-number":"nct03914326","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6141-634X","authenticated-orcid":true,"given":"Nikolaus","family":"Marx","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I, Rheinisch-Westf\u00e4lische Technische Hochschule Aachen University, University Hospital Aachen, Germany (N.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Deanfield","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences, University College London, United Kingdom (J.E.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes F.E.","family":"Mann","sequence":"additional","affiliation":[{"name":"Kuratorium f\u00fcr Heimdialyse Kidney Center, Munich, Germany (J.F.E.M.)."},{"name":"Friedrich Alexander University of Erlangen, Germany (J.F.E.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario","family":"Arechavaleta","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Universidad Autonoma de Guadalajara, Jalisco, Mexico (R.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8519-4964","authenticated-orcid":true,"given":"Stephen C.","family":"Bain","sequence":"additional","affiliation":[{"name":"School of Medicine, Swansea University, United Kingdom (S.C.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1461-1465","authenticated-orcid":true,"given":"Harpreet S.","family":"Bajaj","sequence":"additional","affiliation":[{"name":"LMC Diabetes and Endocrinology, Brampton, Canada (H.S.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrine","family":"Bayer Tanggaard","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, S\u00f8borg, Denmark (K.B.-T., Z.D.-E., M.D.M.E., G.K.H., S.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1407-9023","authenticated-orcid":true,"given":"Andreas L.","family":"Birkenfeld","sequence":"additional","affiliation":[{"name":"Department of Diabetology, Endocrinology and Nephrology, University Hospital T\u00fcbingen, Germany (A.L.B.)."},{"name":"Institute for Diabetes Research and Metabolic Diseases, Helmholtz Munich, German Center for Diabetes Research (A.L.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9723-3876","authenticated-orcid":true,"given":"John B.","family":"Buse","sequence":"additional","affiliation":[{"name":"University of North Carolina School of Medicine, Chapel Hill (J.B.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaklina","family":"Davicevic-Elez","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, S\u00f8borg, Denmark (K.B.-T., Z.D.-E., M.D.M.E., G.K.H., S.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6660-0568","authenticated-orcid":true,"given":"Cyrus","family":"Desouza","sequence":"additional","affiliation":[{"name":"Division of Diabetes, Endocrinology, and Metabolism, Department of Internal Medicine, University of Nebraska Medical Center, Omaha (C.D.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott 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