{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:51:02Z","timestamp":1753890662736,"version":"3.41.2"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>The cardiorenal benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) are established, whereas those in patients without T2DM are not established. We sought to assess the cardiorenal efficacy and safety of SGLT2 inhibitors in non-T2DM patients by performing a meta-analysis based on the subgroup data of non-T2DM patients from relevant secondary analysis articles in which subgroup analyses were done according to the status of diabetes. Compared to placebo, SGLT2 inhibitors significantly reduced heart failure hospitalization [risk ratio (RR) 0.70, 95% confidence interval (CI) 0.59\u20130.83] and kidney-specific composite outcome (RR 0.55, 95% CI 0.40\u20130.75) and increased Kansas City Cardiomyopathy Questionnaire total score by 1.15 (95% CI 1.05\u20131.25) in patients without T2DM with heart failure (HF) or chronic kidney disease (CKD), whereas gliflozins did not significantly affect cardiovascular death, all-cause mortality, volume depletion, fracture, and amputation in this vulnerable population. There was no event of major hypoglycemia or diabetic ketoacidosis observed in the non-T2DM subgroup in included trials. These findings will further prompt gliflozins to be used for the prevention of HF and renal failure events and for the improvement of life quality in patients without T2DM with HF or CKD.<\/jats:p>","DOI":"10.3389\/fcvm.2021.690529","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T04:38:29Z","timestamp":1625027909000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Meta-Analysis on the Safety and Cardiorenal Efficacy of SGLT2 Inhibitors in Patients Without T2DM"],"prefix":"10.3389","volume":"8","author":[{"given":"Lu-Feng","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang-Liang","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ze-Lin","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,30]]},"reference":[{"key":"B1","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."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2295","DOI":"10.1056\/NEJMoa1811744","article-title":"Canagliflozin and renal outcomes in type 2 diabetes and nephropathy","volume":"380","author":"Perkovic","year":"2019","journal-title":"N Engl J Med."},{"key":"B3","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."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1056\/NEJMoa2004967","article-title":"Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes","volume":"383","author":"Cannon","year":"2020","journal-title":"N Engl J Med."},{"key":"B5","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":"B6","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1056\/NEJMoa2022190","article-title":"Cardiovascular and renal outcomes with empagliflozin in heart failure","volume":"383","author":"Packer","year":"2020","journal-title":"N Engl J Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1995","DOI":"10.1056\/NEJMoa1911303","article-title":"Dapagliflozin in patients with heart failure and reduced ejection fraction","volume":"381","author":"Mcmurray","year":"2019","journal-title":"N Engl J Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1056\/NEJMoa2024816","article-title":"Dapagliflozin in patients with chronic kidney disease","volume":"383","author":"Heerspink","year":"2020","journal-title":"N Engl J Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"487","DOI":"10.2337\/dci19-0066","article-title":"2019 update to: management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American diabetes association (ADA) and the European association for the study of diabetes (EASD)","volume":"43","author":"Buse","year":"2020","journal-title":"Diabetes Care."},{"key":"B10","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1093\/eurheartj\/ehz486","article-title":"2019 ESC Guidelines on diabetes, pre-diabetes, cardiovascular diseases developed in collaboration with the EASD","volume":"41","author":"Cosentino","year":"2020","journal-title":"Eur Heart J."},{"key":"B11","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/S2213-8587(20)30343-0","article-title":"Guideline recommendations and the positioning of newer drugs in type 2 diabetes care","volume":"9","author":"Marx","year":"2021","journal-title":"Lancet Diabetes Endocrinol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/S2213-8587(20)30369-7","article-title":"Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial","volume":"9","author":"Wheeler","year":"2021","journal-title":"Lancet Diabetes Endocrinol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1055\/s-0041-1727472","article-title":"Effect of empagliflozin on cardiovascular and renal outcomes in patients with heart failure by baseline diabetes status: results from the emperor-reduced trial","volume":"143","author":"Anker","year":"2021","journal-title":"Circulation."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1001\/jama.2019.22087","article-title":"Effect of dapagliflozin on worsening heart failure and cardiovascular death in patients with heart failure with and without diabetes","volume":"323","author":"Petrie","year":"2020","journal-title":"JAMA."},{"key":"B15","doi-asserted-by":"publisher","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The cochrane collaboration's tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"BMJ."},{"key":"B16","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/S0140-6736(18)32590-X","article-title":"SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials","volume":"393","author":"Zelniker","year":"2019","journal-title":"Lancet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1016\/S2213-8587(19)30256-6","article-title":"SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis","volume":"7","author":"Neuen","year":"2019","journal-title":"Lancet Diabetes Endocrinol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2429","DOI":"10.1007\/s13300-020-00912-z","article-title":"GLP-1RAs and SGLT2is reduce cardiovascular events independent of reductions of systolic blood pressure and body weight: a meta-analysis with meta-regression","volume":"11","author":"Qiu","year":"2020","journal-title":"Diabetes Ther."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e14908","DOI":"10.1161\/JAHA.119.014908","article-title":"Sodium-Glucose cotransporter 2 inhibition for the prevention of cardiovascular events in patients with type 2 diabetes mellitus: a systematic review and meta-analysis","volume":"9","author":"Arnott","year":"2020","journal-title":"J Am Heart Assoc."},{"key":"B20","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1001\/jamacardio.2020.4511","article-title":"Association of SGLT2 inhibitors with cardiovascular and kidney outcomes in patients with type 2 diabetes: a meta-analysis","volume":"6","author":"Mcguire","year":"2021","journal-title":"JAMA Cardiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/S0140-6736(20)31824-9","article-title":"SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials","volume":"396","author":"Zannad","year":"2020","journal-title":"Lancet."},{"key":"B22","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejim.2021.03.020","article-title":"Effect of SGLT-2 inhibitors on cardiovascular outcomes in heart failure patients: a meta-analysis of randomized controlled trials","volume-title":"Eur J Intern Med.","author":"Lu","year":"2021"},{"key":"B23","doi-asserted-by":"publisher","first-page":"3298","DOI":"10.1002\/ehf2.13169","article-title":"Efficacy and safety of SGLT2 inhibitors in heart failure: systematic review and meta-analysis","volume":"7","author":"Butler","year":"2020","journal-title":"ESC Heart Fail."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e019463","DOI":"10.1161\/JAHA.120.019463","article-title":"Effects of sodium\/glucose cotransporter 2 (SGLT2) inhibitors on cardiovascular and metabolic outcomes in patients without diabetes mellitus: a systematic review and meta-analysis of randomized-controlled trials","volume":"10","author":"Teo","year":"2021","journal-title":"J Am Heart Assoc."},{"key":"B25","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.jacc.2019.11.031","article-title":"Mechanisms of Cardiorenal effects of sodium-glucose cotransporter 2 inhibitors: JACC State-of-the-art review","volume":"75","author":"Zelniker","year":"2020","journal-title":"J Am Coll Cardiol."}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2021.690529\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T02:15:58Z","timestamp":1672625758000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2021.690529\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,30]]},"references-count":25,"alternative-id":["10.3389\/fcvm.2021.690529"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2021.690529","relation":{},"ISSN":["2297-055X"],"issn-type":[{"type":"electronic","value":"2297-055X"}],"subject":[],"published":{"date-parts":[[2021,6,30]]},"article-number":"690529"}}