{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T02:33:35Z","timestamp":1793932415640,"version":"4.8.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Adv Ther"],"published-print":{"date-parts":[[2024,7]]},"DOI":"10.1007\/s12325-024-02879-w","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T08:01:31Z","timestamp":1716278491000},"page":"2826-2844","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Safety of Empagliflozin: An Individual Participant-Level Data Meta-Analysis from Four Large Trials"],"prefix":"10.1007","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9507-5301","authenticated-orcid":false,"given":"Christoph","family":"Wanner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hristo","family":"Iliev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalia","family":"Duarte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5955-8303","authenticated-orcid":false,"given":"Elke","family":"Schueler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Rita","family":"Soares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikram","family":"Thanam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7799-1733","authenticated-orcid":false,"given":"Egon","family":"Pfarr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,21]]},"reference":[{"key":"2879_CR1","doi-asserted-by":"publisher","first-page":"2117","DOI":"10.1056\/NEJMoa1504720","volume":"373","author":"B Zinman","year":"2015","unstructured":"Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117\u201328.","journal-title":"N Engl J Med"},{"key":"2879_CR2","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1056\/NEJMoa2107038","volume":"385","author":"SD Anker","year":"2021","unstructured":"Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385:1451\u201361.","journal-title":"N Engl J Med"},{"key":"2879_CR3","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1056\/NEJMoa2204233","volume":"388","author":"WG Herrington","year":"2023","unstructured":"Herrington WG, Staplin N, Wanner C, et al. Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2023;388:117\u201327.","journal-title":"N Engl J Med"},{"key":"2879_CR4","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1056\/NEJMoa2022190","volume":"383","author":"M Packer","year":"2020","unstructured":"Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383:1413\u201324.","journal-title":"N Engl J Med"},{"key":"2879_CR5","unstructured":"Boehringer Ingelheim Limited. Jardiance 10\u00a0mg film-coated tablets. Summary of Product Characteristics, Updated 14 Sep 2023. https:\/\/www.medicines.org.uk\/emc\/product\/5441\/smpc#about-medicine. Accessed 8 Feb 2024."},{"key":"2879_CR6","doi-asserted-by":"publisher","first-page":"3463","DOI":"10.1007\/s12325-020-01329-7","volume":"37","author":"O Kinduryte Schorling","year":"2020","unstructured":"Kinduryte Schorling O, Clark D, Zwiener I, Kaspers S, Lee J, Iliev H. Pooled safety and tolerability analysis of empagliflozin in patients with type 2 diabetes mellitus. Adv Ther. 2020;37:3463\u201384.","journal-title":"Adv Ther"},{"key":"2879_CR7","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1016\/j.clinthera.2016.03.031","volume":"38","author":"S Kohler","year":"2016","unstructured":"Kohler S, Salsali A, Hantel S, et al. Safety and tolerability of empagliflozin in patients with type 2 diabetes. Clin Ther. 2016;38:1299\u2013313.","journal-title":"Clin Ther"},{"key":"2879_CR8","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.1007\/s12325-017-0573-0","volume":"34","author":"S Kohler","year":"2017","unstructured":"Kohler S, Zeller C, Iliev H, Kaspers S. Safety and tolerability of empagliflozin in patients with type 2 diabetes: pooled analysis of phase I\u2013III clinical trials. Adv Ther. 2017;34:1707\u201326.","journal-title":"Adv Ther"},{"key":"2879_CR9","unstructured":"Nuffield Department of Population Health Renal Studies G, Consortium SiM-AC-RT. Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. Lancet. 2022; 400:1788\u2013801."},{"key":"2879_CR10","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.2337\/dc21-2034","volume":"45","author":"KR Tuttle","year":"2022","unstructured":"Tuttle KR, Levin A, Nangaku M, et al. Safety of empagliflozin in patients with type 2 diabetes and chronic kidney disease: pooled analysis of placebo-controlled clinical trials. Diabetes Care. 2022;45:1445\u201352.","journal-title":"Diabetes Care"},{"key":"2879_CR11","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1111\/joim.12244","volume":"276","author":"MA Abdul-Ghani","year":"2014","unstructured":"Abdul-Ghani MA, DeFronzo RA. Lowering plasma glucose concentration by inhibiting renal sodium-glucose cotransport. J Intern Med. 2014;276:352\u201363.","journal-title":"J Intern Med"},{"key":"2879_CR12","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2021.101163","volume":"41","author":"N Staplin","year":"2021","unstructured":"Staplin N, Roddick AJ, Emberson J, et al. Net effects of sodium-glucose co-transporter-2 inhibition in different patient groups: a meta-analysis of large placebo-controlled randomized trials. EClinicalMedicine. 2021;41: 101163.","journal-title":"EClinicalMedicine"},{"key":"2879_CR13","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2018-022577","volume":"9","author":"JR Donnan","year":"2019","unstructured":"Donnan JR, Grandy CA, Chibrikov E, et al. Comparative safety of the sodium glucose co-transporter 2 (SGLT2) inhibitors: a systematic review and meta-analysis. BMJ Open. 2019;9: e022577.","journal-title":"BMJ Open"},{"key":"2879_CR14","doi-asserted-by":"publisher","first-page":"e4","DOI":"10.2337\/dc17-1551","volume":"41","author":"SE Inzucchi","year":"2018","unstructured":"Inzucchi SE, Iliev H, Pfarr E, Zinman B. Empagliflozin and assessment of lower-limb amputations in the EMPA-REG OUTCOME trial. Diabetes Care. 2018;41:e4\u20135.","journal-title":"Diabetes Care"},{"key":"2879_CR15","doi-asserted-by":"publisher","first-page":"782","DOI":"10.4158\/EP.14.6.782","volume":"14","author":"MA Abdul-Ghani","year":"2008","unstructured":"Abdul-Ghani MA, DeFronzo RA. Inhibition of renal glucose reabsorption: a novel strategy for achieving glucose control in type 2 diabetes mellitus. Endocr Pract. 2008;14:782\u201390.","journal-title":"Endocr Pract"},{"key":"2879_CR16","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s40265-014-0337-y","volume":"75","author":"AJ Scheen","year":"2015","unstructured":"Scheen AJ. Pharmacodynamics, efficacy and safety of sodium-glucose co-transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus. Drugs. 2015;75:33\u201359.","journal-title":"Drugs"},{"key":"2879_CR17","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.2215\/CJN.17621120","volume":"16","author":"BF Palmer","year":"2021","unstructured":"Palmer BF, Clegg DJ. Euglycemic ketoacidosis as a complication of SGLT2 inhibitor therapy. Clin J Am Soc Nephrol. 2021;16:1284\u201391.","journal-title":"Clin J Am Soc Nephrol"},{"key":"2879_CR18","doi-asserted-by":"publisher","first-page":"2265","DOI":"10.1016\/j.clinthera.2016.09.001","volume":"38","author":"T Heise","year":"2016","unstructured":"Heise T, Jordan J, Wanner C, et al. Pharmacodynamic effects of single and multiple doses of empagliflozin in patients with type 2 diabetes. Clin Ther. 2016;38:2265\u201376.","journal-title":"Clin Ther"},{"key":"2879_CR19","doi-asserted-by":"publisher","first-page":"2099","DOI":"10.1056\/NEJMoa1611925","volume":"377","author":"B Neal","year":"2017","unstructured":"Neal B, Perkovic V, Matthews DR. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:2099.","journal-title":"N Engl J Med"},{"key":"2879_CR20","doi-asserted-by":"publisher","first-page":"2295","DOI":"10.1056\/NEJMoa1811744","volume":"380","author":"V Perkovic","year":"2019","unstructured":"Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380:2295\u2013306.","journal-title":"N Engl J Med"}],"container-title":["Advances in Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12325-024-02879-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12325-024-02879-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12325-024-02879-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T10:30:28Z","timestamp":1719570628000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12325-024-02879-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,21]]},"references-count":20,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["2879"],"URL":"https:\/\/doi.org\/10.1007\/s12325-024-02879-w","relation":{},"ISSN":["0741-238X","1865-8652"],"issn-type":[{"value":"0741-238X","type":"print"},{"value":"1865-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,21]]},"assertion":[{"value":"4 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 April 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Christoph Wanner has received personal fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, CSL-Vifor, Eli Lilly and Company, GlaxoSmithKline, MSD, Novo Nordisk, Novartis, and Sanofi. Hristo Iliev is an employee of Boehringer Ingelheim. Vikram Thanam is an employee of Boehringer Ingelheim. Elke Schueler is employee of mainanalytics GmbH, working on behalf of Boehringer Ingelheim Pharma GmbH & Co. KG. Egon Pfarr is an employee of Boehringer Ingelheim. Ana Rita Soares is an employee of Eli Lilly and Company. Nathalia Duarte is an employee of Boehringer Ingelheim.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"The ethics committee at each center approved the trials, and all patients provided written informed consent. All original trials were performed in accordance with the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}]}}