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This paper will briefly compare the effect of SGLT2is and GLP-1 RAs to that of the SGLT1\/2 inhibitor sotagliflozin on the incidence of myocardial infarction (MI) and stroke in patients with T2DM and further postulate mechanisms to account for these findings.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods and Results<\/jats:title>\n                <jats:p>Thus far, the results from SCORED and SOLOIST (trials studying the SGLT1\/2 inhibitor sotagliflozin) suggest that an increase in SGLT1 inhibition when added to SGLT2 inhibition may contribute to reductions in MI and stroke in patients with T2DM. This benefit is beyond what SGLT2is alone can accomplish and at least similar to GLP-1 RAs but with the added benefit of a reduction in hospitalizations and urgent visits for HF. Larger and longer studies are required to confirm the effectiveness of SGLT1\/SGLT2 inhibition in reducing MI and stroke in patients with T2DM and elucidate the mechanisms associated with this finding.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The role of SGLT1\/2 inhibition as an addition to GLP-1 RAs in patients with and without T2DM at increased risk for MI and stroke requires further study. Regardless, the finding that a relative increase in SGLT1\/2 inhibition reduces the risk of MI and stroke as well as hospitalizations and urgent visits for heart failure could improve quality of life and reduce the healthcare burden associated with T2DM.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10557-021-07291-y","type":"journal-article","created":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T03:02:31Z","timestamp":1636426951000},"page":"561-567","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["The Role of Combined SGLT1\/SGLT2 Inhibition in Reducing the Incidence of Stroke and Myocardial Infarction in Patients with Type 2 Diabetes Mellitus"],"prefix":"10.1007","volume":"36","author":[{"given":"Bertram","family":"Pitt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Steg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence A.","family":"Leiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1278-6245","authenticated-orcid":false,"given":"Deepak L.","family":"Bhatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,9]]},"reference":[{"key":"7291_CR1","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1016\/j.jacc.2020.05.037","volume":"76","author":"SR Das","year":"2020","unstructured":"Das SR, Everett BM, Birtcher KK, et al. 2020 Expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes. 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Ann Intern Med. 2021 Jun 22.","DOI":"10.7326\/M21-0651"}],"updated-by":[{"DOI":"10.1007\/s10557-021-07308-6","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T00:00:00Z","timestamp":1640304000000}}],"container-title":["Cardiovascular Drugs and Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10557-021-07291-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10557-021-07291-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10557-021-07291-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T08:19:20Z","timestamp":1652170760000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10557-021-07291-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,9]]},"references-count":49,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["7291"],"URL":"https:\/\/doi.org\/10.1007\/s10557-021-07291-y","relation":{"correction":[{"id-type":"doi","id":"10.1007\/s10557-021-07308-6","asserted-by":"object"}]},"ISSN":["0920-3206","1573-7241"],"issn-type":[{"value":"0920-3206","type":"print"},{"value":"1573-7241","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,9]]},"assertion":[{"value":"4 November 2021","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 November 2021","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 December 2021","order":3,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":4,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":5,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1007\/s10557-021-07308-6","URL":"https:\/\/doi.org\/10.1007\/s10557-021-07308-6","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Dr. Pitt served as co-chair of SOLOIST, was on the executive committee of SCORED, and received consulting fees from Sanofi\/Lexicon. In addition, Dr. Pitt discloses the following relationships\u2014consulting fees: Bayer, Astra Zeneca, Boehringer Ingelheim\/Lilly, Merck, and Phasebio. Consulting fees\u2009+\u2009stock options: SCPharmaceuticals, SQinnovations, G3pharmaceuticals, Relypsa\/Vifor, Cereno scientific, KBP Pharmaceuticals, Sarfez, Tricida, Proton Intel, and Brainstorm Medical. He is chairman of the steering committee of the NHLBI TRANSFORM trial and co-chair of the NHLBI\u2013Swedish Heart Foundation SPIRRIT trial. He holds US Patent 9931412 on site specific delivery of eplerenone to the myocardium and pending US Patent 63\/045,784 on histone-acetylation-modulating agents for the treatment and protection of organ damage.Dr. Steg discloses the following relationships: research grant from Amarin, Bayer, Sanofi, and Servier; speaking or consulting fees from Amarin, Amgen, AstraZeneca, Bayer\/Janssen, Bristol-Myers-Squibb, Idorsia, Myokardia, Novartis, Novo-Nordisk, PhaseBio, Pfizer, Regeneron, Sanofi, Servier.Dr. Leiter was a member of the Executive Committee of SOLOIST and SCORED and received research funding from, provided CME on behalf of, and\/or acted as an adviser to AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Lexicon, Merck, Novo Nordisk, Sanofi, and Servier.Dr. Bhatt served as the chair of SOLOIST and SCORED, with research funding from Sanofi and then Lexicon paid to Brigham and Women\u2019s Hospital. Dr. Bhatt discloses the following relationships\u2014advisory board: Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Janssen, Level Ex, Medscape Cardiology, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, Stasys; board of directors: Boston VA Research Institute, Society of Cardiovascular Patient Care, TobeSoft; chair: inaugural chair, American Heart Association Quality Oversight Committee; data monitoring committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), Novartis, Population Health Research Institute; honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi\/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence\/ReachMD (CME steering committees), MJH Life Sciences, Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today\u2019s Intervention), Society of Cardiovascular Patient Care (Secretary\/Treasurer), WebMD (CME steering committees); other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); research funding: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Lexicon, Lilly, Medtronic, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, 89Bio; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald\u2019s Heart Disease); site co-investigator: Abbott, Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Philips, Svelte; Trustee: American College of Cardiology; unfunded research: FlowCo, Merck, Takeda.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}