{
    "abstract": "Sodium-glucose co-transporter (SGLT)-2 inhibitors have shown consistent benefit in improving heart failure-related outcomes but not ischaemic cardiovascular events such as myocardial infarction or stroke. We assessed if the dual SGLT1/2 inhibitor sotagliflozin improves ischaemic outcomes.\nWe did a prespecified secondary analysis of the SCORED trial, which was a double-blind, placebo-controlled, randomised clinical trial enrolling patients (aged \u226518 years) with type 2 diabetes, chronic kidney disease (estimated glomerular filtration rate [eGFR] 25-60 mL/min per 1\u00b773 m\n10 584 patients were enrolled and randomly assigned to sotagliflozin (n=5292 [50\u00b70%]) or placebo (n=5292 [50\u00b70%]) between Dec 8, 2017 and Jan 20, 2020 (median age 69 years [IQR 63-74]; 4754 [44\u00b79%] female patients and 5830 [55\u00b71%] male patients). 5144 (48\u00b76%) patients had a history of cardiovascular disease, of whom 2108 (19\u00b79% of the total population) had a history of myocardial infarction, 946 (8\u00b79%) had a history of stroke, and 2375 (22\u00b74%) had a history of coronary revascularisation. Patients in the sotagliflozin group had a significantly lower rate of total MACE than those in the placebo group (4\u00b78 events per 100 person-years vs 6\u00b73 events per 100 person-years; hazard ratio [HR] 0\u00b777 [95% CI 0\u00b765-0\u00b791]; p=0\u00b70020). Interaction analyses suggested a consistent effect of sotagliflozin on total MACE among stratified subgroups without evidence of heterogeneity. Additionally, sotagliflozin significantly reduced the rate of myocardial infarction (1\u00b78 events per 100 person-years vs 2\u00b77 events per 100 person-years; HR 0\u00b768 [0\u00b752-0\u00b789]; p=0\u00b70041) and stroke (1\u00b72 events per 100 person-years vs 1\u00b78 events per 100 person-years; HR 0\u00b766 [0\u00b748-0\u00b791]; p=0\u00b7012) compared with placebo.\nSotagliflozin reduced MACE, with independent reductions in myocardial infarction and stroke, among patients with type 2 diabetes, chronic kidney disease, and additional cardiovascular risk. The ischaemic benefit on both myocardial infarction and stroke has not been previously observed with other SGLT inhibitors and warrants investigation of combined SGLT1 and SGLT2 inhibition as a possible underlying mechanism.\nLexicon Pharmaceuticals.",
    "authors": [
        {
            "affiliation": "Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, Boston, MA, USA.",
            "firstname": "Rahul",
            "initials": "R",
            "lastname": "Aggarwal"
        },
        {
            "affiliation": "Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: dlbhattmd@post.harvard.edu.",
            "firstname": "Deepak L",
            "initials": "DL",
            "lastname": "Bhatt"
        },
        {
            "affiliation": "Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA; CPC Clinical Research and University of Colorado Anschutz Medical Campus, Aurora, CO, USA; State University of New York Downstate School of Public Health, Brooklyn, NY, USA.",
            "firstname": "Michael",
            "initials": "M",
            "lastname": "Szarek"
        },
        {
            "affiliation": "Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, Boston, MA, USA.",
            "firstname": "Christopher P",
            "initials": "CP",
            "lastname": "Cannon"
        },
        {
            "affiliation": "Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto, Toronto, ON, Canada.",
            "firstname": "Lawrence A",
            "initials": "LA",
            "lastname": "Leiter"
        },
        {
            "affiliation": "Yale School of Medicine, New Haven, CT, USA.",
            "firstname": "Silvio E",
            "initials": "SE",
            "lastname": "Inzucchi"
        },
        {
            "affiliation": "Duke University School of Medicine, Durham, NC, USA.",
            "firstname": "Renato D",
            "initials": "RD",
            "lastname": "Lopes"
        },
        {
            "affiliation": "University of Texas Southwestern Medical Center and Parkland Health, Dallas, Texas, USA.",
            "firstname": "Darren K",
            "initials": "DK",
            "lastname": "McGuire"
        },
        {
            "affiliation": "Vanderbilt University Medical Center, Nashville, Tennessee, USA.",
            "firstname": "Julia B",
            "initials": "JB",
            "lastname": "Lewis"
        },
        {
            "affiliation": "Oregon Health and Science University, Portland, OR, USA.",
            "firstname": "Matthew C",
            "initials": "MC",
            "lastname": "Riddle"
        },
        {
            "affiliation": "Lexicon Pharmaceuticals, The Woodlands, TX, USA.",
            "firstname": "Michael J",
            "initials": "MJ",
            "lastname": "Davies"
        },
        {
            "affiliation": "Lexicon Pharmaceuticals, The Woodlands, TX, USA.",
            "firstname": "Phillip",
            "initials": "P",
            "lastname": "Banks"
        },
        {
            "affiliation": "Lexicon Pharmaceuticals, The Woodlands, TX, USA.",
            "firstname": "Amy K",
            "initials": "AK",
            "lastname": "Carroll"
        },
        {
            "affiliation": "TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.",
            "firstname": "Benjamin M",
            "initials": "BM",
            "lastname": "Scirica"
        },
        {
            "affiliation": "Department of Primary Care and Public Health, Imperial College London, London, UK.",
            "firstname": "Kausik K",
            "initials": "KK",
            "lastname": "Ray"
        },
        {
            "affiliation": "Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, MO, USA.",
            "firstname": "Mikhail N",
            "initials": "MN",
            "lastname": "Kosiborod"
        },
        {
            "affiliation": "University Health Network, Toronto General Hospital Research Institute, University of Toronto, Toronto, ON, Canada.",
            "firstname": "David Z I",
            "initials": "DZI",
            "lastname": "Cherney"
        },
        {
            "affiliation": "Women's College Hospital and Peter Munk Cardiac Centre, Toronto General Hospital, University of Toronto, ON, Canada.",
            "firstname": "Jacob A",
            "initials": "JA",
            "lastname": "Udell"
        },
        {
            "affiliation": "Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto, Toronto, ON, Canada.",
            "firstname": "Subodh",
            "initials": "S",
            "lastname": "Verma"
        },
        {
            "affiliation": "Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, Boston, MA, USA; Elucida Research, Beverly, MA, USA.",
            "firstname": "R Preston",
            "initials": "RP",
            "lastname": "Mason"
        },
        {
            "affiliation": "University of Michigan, Ann Arbor, MI, USA.",
            "firstname": "Bertram",
            "initials": "B",
            "lastname": "Pitt"
        },
        {
            "affiliation": "Universit\u00e9 Paris-Cit\u00e9, INSERM U1148 and AP-HP H\u00f4pital Bichat, Paris, France; French Alliance for Cardiovascular Trials, Paris, France.",
            "firstname": "Ph Gabriel",
            "initials": "PG",
            "lastname": "Steg"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00a9 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.",
    "doi": "10.1016/S2213-8587(24)00362-0",
    "journal": "The lancet. Diabetes & endocrinology",
    "keywords": [],
    "methods": null,
    "publication_date": "2025-02-18",
    "pubmed_id": "39961315",
    "results": null,
    "title": "Effect of sotagliflozin on major adverse cardiovascular events: a prespecified secondary analysis of the SCORED randomised trial.",
    "xml": "<Element 'PubmedArticle' at 0x78850521ddf0>"
}