{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:48Z","timestamp":1792787628311,"version":"4.5.0"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"American Heart Association","award":["PRE1019986"],"award-info":[{"award-number":["PRE1019986"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Lexicon Pharmaceuticals","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"https:\/\/ror.org\/00v64s089","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institutes of Health","award":["T32 GM140223"],"award-info":[{"award-number":["T32 GM140223"]}]},{"name":"National Institutes of Health","award":["T32 TR004371"],"award-info":[{"award-number":["T32 TR004371"]}]},{"name":"National Institutes of Health","award":["F31 HL179940"],"award-info":[{"award-number":["F31 HL179940"]}]},{"name":"National Institutes of Health","award":["R35 HL150784"],"award-info":[{"award-number":["R35 HL150784"]}]},{"name":"National Institutes of Health","award":["R01 HL109946"],"award-info":[{"award-number":["R01 HL109946"]}]},{"name":"Henry and Mala Dorfman Professor of Pediatric Hematology\/Oncology","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    As rates of type 2 diabetes mellitus (T2DM) have risen, comorbidities of T2DM and cardiovascular disease (CVD) have similarly increased. The adoption of sodium-glucose cotransporter (SGLT) 2 inhibitors as a treatment for T2DM has provided an effective means of decreasing renal glucose reabsorption. In recent clinical trials, sotagliflozin, the first FDA-approved inhibitor of both isoforms of SGLT (SGLT1 and SGLT2), demonstrated a reduction in myocardial infarction and stroke in patients with T2DM at high cardiovascular risk. The cardiovascular protective effect of sotagliflozin compared to the SGLT2-selective inhibitor, empagliflozin, was investigated by evaluating effects on platelet activation and thrombus formation. Employing ex vivo models using blood from healthy donors or T2DM patients, and in vivo mouse models, we demonstrate an inhibitory effect on platelet activity and thrombus formation with sotagliflozin, while empagliflozin has minor to no effects. Further, no impact on hemostasis was observed with sotagliflozin. Finally, a platelet-specific deletion of SGLT1 via\n                    <jats:italic>\n                      Slc5a1\n                      <jats:sup>fl\/fl<\/jats:sup>\n                    <\/jats:italic>\n                    <jats:italic>Gp1ba-Cre\u207a<\/jats:italic>\n                    mice resulted in reduced platelet integrin activation and thrombus formation. This study provides insight into a potential explanation for the cardiovascular protection conferred by sotagliflozin observed in patients with T2DM at risk of an ischemic event and reveals an added benefit to SGLT2-selective inhibitors.\n                  <\/jats:p>","DOI":"10.1172\/jci201899","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:06:18Z","timestamp":1792004778000},"source":"Crossref","is-referenced-by-count":0,"title":["SGLT1\/2 inhibitor sotagliflozin, but not SGLT2-selective inhibitor empagliflozin, attenuates platelet activation and thrombosis"],"prefix":"10.1172","author":[{"given":"Livia","family":"Stanger","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Michigan Medical Center, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista","family":"Goerger","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Michigan Medical Center, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja","family":"Yalavarthi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Michigan Medical Center, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Rickenberg","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Michigan Medical Center, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Michigan Medical Center, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariane","family":"Flores Nascimento","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Michigan Medical Center, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashleigh","family":"Kilgore","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Michigan Medical Center, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heeseo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Michigan Medical Center, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaokang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3334-9159","authenticated-orcid":true,"given":"Yanhong","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna R.","family":"Dahlgren","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5161-4705","authenticated-orcid":true,"given":"Jifeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2874-4904","authenticated-orcid":true,"given":"Jordan A.","family":"Shavit","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertram","family":"Pitt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2357-7825","authenticated-orcid":true,"given":"Y. Eugene","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Holinstat","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Michigan Medical Center, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,10,13]]},"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.jci.org\/articles\/view\/201899\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:06:20Z","timestamp":1792004780000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.jci.org\/articles\/view\/201899"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,13]]},"references-count":0,"alternative-id":["10.1172\/JCI201899"],"URL":"https:\/\/doi.org\/10.1172\/jci201899","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,13]]}}}