{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:41:59Z","timestamp":1791384119104,"version":"4.3.3"},"reference-count":51,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Intern Med"],"published-print":{"date-parts":[[2025,3,1]]},"abstract":"<jats:sec id=\"ab-ioi240090-4\"><jats:title>Importance<\/jats:title><jats:p>Evidence on cardiovascular benefits and safety of sodium-glucose cotransporter 2 (SGLT-2) inhibitors is mainly from placebo-controlled trials. Therefore, the comparative effectiveness and safety of individual SGLT-2 inhibitors remain unknown.<\/jats:p><\/jats:sec><jats:sec id=\"ab-ioi240090-5\"><jats:title>Objective<\/jats:title><jats:p>To compare the use of canagliflozin or dapagliflozin with empagliflozin for a composite outcome (myocardial infarction [MI] or stroke), heart failure hospitalization, MI, stroke, all-cause death, and safety outcomes, including diabetic ketoacidosis (DKA), lower-limb amputation, bone fracture, severe urinary tract infection (UTI), and genital infection and whether effects differed by dosage or cardiovascular disease (CVD) history.<\/jats:p><\/jats:sec><jats:sec id=\"ab-ioi240090-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This comparative effectiveness study using target trial emulation included adults with type 2 diabetes (T2D) using 3 US claims databases using data from August 2014 through June 2020. The study was conducted from August 2023 to July 2024, with a follow-up period of up to 8 years, and the analysis was completed in July 2024.<\/jats:p><\/jats:sec><jats:sec id=\"ab-ioi240090-7\"><jats:title>Exposures<\/jats:title><jats:p>First dispensing of canagliflozin, dapagliflozin, or empagliflozin without any use of SGLT-2 inhibitors during the prior 365 days.<\/jats:p><\/jats:sec><jats:sec id=\"ab-ioi240090-8\"><jats:title>Main outcomes and measures<\/jats:title><jats:p>Database-specific models were weighted using propensity score matching-weights to adjust for 129 confounders. Hazard ratios and 95% CIs for outcomes were estimated using weighted Cox proportional hazards models. HRs were pooled across databases using a fixed-effect meta-analysis.<\/jats:p><\/jats:sec><jats:sec id=\"ab-ioi240090-9\"><jats:title>Results<\/jats:title><jats:p>: Across the databases, 232\u202f890 patients receiving canagliflozin, 129\u202f881 patients receiving dapagliflozin, and 295\u202f043 patients receiving empagliflozin were identified. Compared with empagliflozin initiators, those receiving canagliflozin or dapagliflozin were less likely to have diabetes-related conditions or a history of CVD at baseline. For MI\/stroke risk, both canagliflozin (HR, 0.98; 95% CI, 0.91-1.05) and dapagliflozin (HR, 0.95; 95% CI, 0.89-1.03) were comparable to empagliflozin. For heart failure hospitalization, dapagliflozin initiators had a higher risk (HR, 1.19; 95% CI, 1.02-1.39), particularly at the low dose of 5 mg (HR, 1.30; 95% CI, 1.12-1.50). These findings were consistent across subgroups of CVD history. For safety events, compared with empagliflozin, canagliflozin initiators had a lower risk of genital infections (HR, 0.94; 95% CI, 0.91-0.97) but a higher risk of severe UTIs (HR, 1.13; 95% CI, 1.03-1.24), and dapagliflozin initiators had lower risks of genital infections (HR, 0.92; 95% CI, 0.89-0.95) and DKA (HR, 0.78; 95% CI, 0.68-0.90).<\/jats:p><\/jats:sec><jats:sec id=\"ab-ioi240090-10\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>This study found that individual SGLT-2 inhibitors demonstrated comparable cardiovascular effectiveness at clinically effective doses, though low-dose dapagliflozin showed a reduced benefit for heart failure hospitalization compared with empagliflozin.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamainternmed.2024.7357","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T16:13:30Z","timestamp":1737476010000},"page":"302","source":"Crossref","is-referenced-by-count":24,"title":["Comparative Effectiveness of Individual Sodium-Glucose Cotransporter 2 Inhibitors"],"prefix":"10.1001","volume":"185","author":[{"given":"HoJin","family":"Shin","sequence":"first","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"},{"name":"Formally with Brigham and Women\u2019s Hospital, Boston, Massachusetts"},{"name":"Now with: Johnson & Johnson Innovative Medicine, Titusville, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie M.","family":"Paik","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"},{"name":"Division of Renal (Kidney) Medicine, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"},{"name":"New England Geriatric Research Education and Clinical Center, VA Boston Healthcare System, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan M.","family":"Everett","sequence":"additional","affiliation":[{"name":"Divisions of Cardiovascular and Preventive Medicine, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elyse","family":"DiCesare","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Alix","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Glynn","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J.","family":"Wexler","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Diabetes Center and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Patorno","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"22","key":"ioi240090r2","doi-asserted-by":"publisher","first-page":"2117","DOI":"10.1056\/NEJMoa1504720","article-title":"Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes.","volume":"373","author":"Zinman","year":"2015","journal-title":"N Engl J Med"},{"issue":"7","key":"ioi240090r3","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1056\/NEJMoa1611925","article-title":"Canagliflozin and cardiovascular and renal events in type 2 diabetes.","volume":"377","author":"Neal","year":"2017","journal-title":"N Engl J Med"},{"issue":"4","key":"ioi240090r4","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1056\/NEJMoa1812389","article-title":"Dapagliflozin and cardiovascular outcomes in type 2 diabetes.","volume":"380","author":"Wiviott","year":"2019","journal-title":"N Engl J Med"},{"key":"ioi240090r8","doi-asserted-by":"publisher","first-page":"S125","DOI":"10.2337\/dc22-S009","article-title":"9. 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