{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T06:39:59Z","timestamp":1785220799961,"version":"3.55.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T00:00:00Z","timestamp":1568851200000},"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. Pharmacol."],"DOI":"10.3389\/fphar.2019.01066","type":"journal-article","created":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T04:29:21Z","timestamp":1568867361000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Appraisal of Non-Cardiovascular Safety for Sodium\u2013Glucose Co-Transporter 2 Inhibitors: A Systematic Review and Meta-Analysis of Placebo-Controlled Randomized Clinical Trials"],"prefix":"10.3389","volume":"10","author":[{"given":"Fang-Hong","family":"Shi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Hong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-Min","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Yan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Chun","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hou-Wen","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2019,9,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"S73","DOI":"10.2337\/dc18-S008","article-title":"8. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2018","volume":"41","year":"2018","journal-title":"Diabetes Care"},{"key":"B2","doi-asserted-by":"publisher","first-page":"963","DOI":"10.2337\/dc17-1962","article-title":"Global economic burden of diabetes in adults: projections from 2015 to 2030","volume":"41","author":"Bommer","year":"2018","journal-title":"Diabetes Care"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2239","DOI":"10.1016\/S0140-6736(17)30058-2","article-title":"Type 2 diabetes","volume":"389","author":"Chatterjee","year":"2017","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1016\/S0140-6736(16)31678-6","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015","volume":"388","year":"2016","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","first-page":"773","DOI":"10.2337\/db09-9028","article-title":"Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus","volume":"58","author":"Defronzo","year":"2009","journal-title":"Diabetes"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1680","DOI":"10.2337\/dc15-1251","article-title":"Diabetic ketoacidosis and related events in the canagliflozin type 2 diabetes clinical program","volume":"38","author":"Erondu","year":"2015","journal-title":"Diabetes Care"},{"key":"B7","unstructured":"FDA Drug Safety Communication: FDA revises label of diabetes drug canagliflozin (Invokana, Invokamet) to include updates on bone fracture risk and new information on decreased bone mineral density2015"},{"key":"B8","unstructured":"Food and Drug Administration (2015): FDA drug safety communication: FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections2015"},{"key":"B9","unstructured":"Food and Drug Administration (2016): FDA drug safety communication: FDA strengthens kidney warnings for diabetes medicines canaglifozin (Invokana, Invokamet) and dapaglifozin (Farxiga, Xigduo XR)2016"},{"key":"B10","unstructured":"Food and Drug Administration (2017): FDA Drug Safety Communication: FDA confirms increased risk of leg and foot amputations with the diabetes medicine canagliflozin (Invokana, Invokamet, Invokamet XR)2017"},{"key":"B11","unstructured":"FDA warns about rare occurrences of a serious infection of the genital area with SGLT2 inhibitors for diabetes2018"},{"key":"B12","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.diabres.2013.12.052","article-title":"Genital and urinary tract infections in diabetes: impact of pharmacologically induced glucosuria","volume":"103","author":"Geerlings","year":"2014","journal-title":"Diabetes Res. Clin. Pract."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1002\/sim.1186","article-title":"Quantifying heterogeneity in a meta-analysis","volume":"21","author":"Higgins","year":"2002","journal-title":"Stat. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1080\/00325481.2016.1153941","article-title":"Osmotic diuresis with SGLT2 inhibition: analysis of events related to volume reduction in dapagliflozin clinical trials","volume":"128","author":"Johnsson","year":"2016","journal-title":"Postgrad. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.2337\/diacare.21.9.1414","article-title":"Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections","volume":"21","author":"King","year":"1998","journal-title":"Diabetes Care"},{"key":"B16","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1038\/nrendo.2013.102","article-title":"Diabetes and its comorbidities\u2014where east meets west","volume":"9","author":"Kong","year":"2013","journal-title":"Nat. Rev. Endocrinol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2628","DOI":"10.1016\/j.jacc.2018.03.009","article-title":"Cardiovascular events associated with SGLT-2 inhibitors versus other glucose-lowering drugs: the CVD-REAL 2 study","volume":"71","author":"Kosiborod","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1111\/dom.12825","article-title":"Urinary tract and genital infections in patients with type 2 diabetes treated with sodium-glucose co-transporter 2 inhibitors: a meta-analysis of randomized controlled trials","volume":"19","author":"Li","year":"2017","journal-title":"Diabetes Obes. Metab."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000011853","article-title":"Clinical adverse effects of sodium-glucose cotransporter 2 inhibitors: protocol for a systematic review and meta-analysis","volume":"97","author":"Li","year":"2018","journal-title":"Medicine (Baltimore)"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2824","DOI":"10.1038\/s41598-017-02733-w","article-title":"Effects of SGLT2 inhibitors on UTIs and genital infections in type 2 diabetes mellitus: a systematic review and meta-analysis","volume":"7","author":"Liu","year":"2017","journal-title":"Sci. Rep."},{"key":"B21","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.diabres.2017.04.017","article-title":"Effects of SGLT-2 inhibitors on diabetic ketoacidosis: a meta-analysis of randomised controlled trials","volume":"130","author":"Monami","year":"2017","journal-title":"Diabetes Res. Clin. Pract."},{"key":"B22","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":"B23","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1042\/CS20171298","article-title":"SGLT2 inhibition and kidney protection","volume":"132","author":"Nespoux","year":"2018","journal-title":"Clin. Sci. (Lond.)"},{"key":"B24","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1111\/dom.12889","article-title":"Novel oral glucose-lowering drugs are associated with lower risk of all-cause mortality, cardiovascular events and severe hypoglycaemia compared with insulin in patients with type 2 diabetes","volume":"19","author":"Nystrom","year":"2017","journal-title":"Diabetes Obes. Metab."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1016\/j.numecd.2017.10.011","article-title":"Acute renal failure with sodium-glucose-cotransporter-2 inhibitors: analysis of the FDA adverse event report system database","volume":"27","author":"Perlman","year":"2017","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.2337\/dc15-0843","article-title":"Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition","volume":"38","author":"Peters","year":"2015","journal-title":"Diabetes Care"},{"key":"B27","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1007\/s00592-018-1116-0","article-title":"SGLT-2 inhibitors and the risk of infections: a systematic review and meta-analysis of randomized controlled trials","volume":"55","author":"Puckrin","year":"2018","journal-title":"Acta Diabetol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.diabres.2018.03.027","article-title":"Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular disease, death and safety outcomes in type 2 diabetes\u2014a systematic review","volume":"140","author":"Radholm","year":"2018","journal-title":"Diabetes Res. Clin. Pract."},{"key":"B29","doi-asserted-by":"publisher","first-page":"g7647","DOI":"10.1136\/bmj.g7647","article-title":"Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation","volume":"350","author":"Shamseer","year":"2015","journal-title":"BMJ"},{"key":"B30","doi-asserted-by":"publisher","first-page":"6","DOI":"10.2337\/dc17-1223","article-title":"Lower risk of death with SGLT2 inhibitors in observational studies: real or bias","volume":"41","author":"Suissa","year":"2018","journal-title":"Diabetes Care"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1774","DOI":"10.1016\/j.amjcard.2016.08.061","article-title":"Meta-analysis of effects of sodium-glucose cotransporter 2 inhibitors on cardiovascular outcomes and all-cause mortality among patients with type 2 diabetes mellitus","volume":"118","author":"Tang","year":"2016","journal-title":"Am. J. Cardiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1111\/dom.12917","article-title":"Sodium-glucose co-transporter-2 inhibitors and risk of adverse renal outcomes among patients with type 2 diabetes: a network and cumulative meta-analysis of randomized controlled trials","volume":"19","author":"Tang","year":"2017","journal-title":"Diabetes Obes. Metab."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2098","DOI":"10.1007\/s00125-018-4669-0","article-title":"The actions of SGLT2 inhibitors on metabolism, renal function and blood pressure","volume":"61","author":"Thomas","year":"2018","journal-title":"Diabetologia"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.dsx.2018.06.003","article-title":"SGLT2 inhibitors and the kidney: effects and mechanisms","volume":"12","author":"Tsimihodimos","year":"2018","journal-title":"Diabetes Metab. Syndr."},{"key":"B35","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1177\/2047487318755531","article-title":"Sodium-glucose co-transporter 2 inhibitors and cardiovascular outcomes: a systematic review and meta-analysis","volume":"25","author":"Usman","year":"2018","journal-title":"Eur. J. Prev. Cardiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/S2213-8587(16)00052-8","article-title":"Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular events, death, and major safety outcomes in adults with type 2 diabetes: a systematic review and meta-analysis","volume":"4","author":"Wu","year":"2016","journal-title":"Lancet Diabetes Endocrinol."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.3405","article-title":"Effects of sodium-glucose co-transporter 2 (SGLT2) inhibition on renal function and albuminuria in patients with type 2 diabetes: a systematic review and meta-analysis","volume":"5","author":"Xu","year":"2017","journal-title":"PeerJ"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.007165","article-title":"Cardiovascular safety, long-term noncardiovascular safety, and efficacy of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus: a systemic review and meta-analysis with trial sequential analysis","volume":"7","author":"Zhang","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"B39","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1111\/dom.13101","article-title":"Effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on serum uric acid level: a meta-analysis of randomized controlled trials","volume":"20","author":"Zhao","year":"2018","journal-title":"Diabetes Obes. Metab."},{"key":"B40","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."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2019.01066\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,20]],"date-time":"2019-09-20T12:58:40Z","timestamp":1568984320000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2019.01066\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,19]]},"references-count":40,"alternative-id":["10.3389\/fphar.2019.01066"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2019.01066","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,19]]},"article-number":"1066"}}