{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T07:38:11Z","timestamp":1769499491468,"version":"3.49.0"},"reference-count":77,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,3,14]],"date-time":"2014-03-14T00:00:00Z","timestamp":1394755200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"LifeScience Research Board - The Defence Research and Development Organisation","award":["DLS\/81\/48222\/LSRB-216\/BTB\/2010"],"award-info":[{"award-number":["DLS\/81\/48222\/LSRB-216\/BTB\/2010"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicinal Research Reviews"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic hyperglycemia is a characteristic feature of type 2 diabetes mellitus (T2DM). The kidney plays a vital role in maintaining blood glucose homeostasis by recovering glucose from glomerular filtrate which is controlled by SGLT2 cotransporters expressed mainly in proximal tubule. In T2DM patients, inhibition of SGLT2 normalizes glycemic levels by preventing glucose from being reabsorbed through SGLT2 and re\u2010entering the circulation. Thus, SGLT2 inhibition seems to be a logical approach and pose a novel insulin\u2010independent mechanism of action for management of T2DM by promoting urinary glucose excretion in the body. Canagliflozin is the first SGLT2 inhibitor approved by US Food and Drug Administration (US FDA) followed by dapagliflozin while empagliflozin is under FDA review. Various other drug candidates in late\u2010stage clinical developments are also expected to hit the global markets in the coming years. In this review, studies on various early\u2010 and late\u2010stage SGLT2 inhibitors have been investigated and recent clinical developments summarized.<\/jats:p>","DOI":"10.1002\/med.21314","type":"journal-article","created":{"date-parts":[[2014,3,14]],"date-time":"2014-03-14T19:32:16Z","timestamp":1394825536000},"page":"1146-1167","source":"Crossref","is-referenced-by-count":10,"title":["Ramping Glucosuria for Management of Type 2 Diabetes Mellitus: An Emerging Cynosure"],"prefix":"10.1002","volume":"34","author":[{"given":"Priyanka","family":"Malla","sequence":"first","affiliation":[{"name":"University Institute of Pharmaceutical Sciences Panjab University  Chandigarh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajnish","family":"Kumar","sequence":"additional","affiliation":[{"name":"University Institute of Pharmaceutical Sciences Panjab University  Chandigarh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manoj K.","family":"Mahapatra","sequence":"additional","affiliation":[{"name":"University Institute of Pharmaceutical Sciences Panjab University  Chandigarh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manoj","family":"Kumar","sequence":"additional","affiliation":[{"name":"University Institute of Pharmaceutical Sciences Panjab University  Chandigarh India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,3,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10761"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2013.54"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/diaclin.26.2.77"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aer120"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(13)70050-0"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2008.00982.x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2010-0029"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3180"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen\u20102012\u2010001007"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-S062"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-012-9352-3"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfh426"},{"key":"e_1_2_11_14_1","unstructured":"Available at:http:\/\/www.fda.gov\/downloads\/AdvisoryCommittees\/CommitteesMeetingMaterials\/Drugs\/EndocrinologicandMetabolicDrugsAdvisoryCommittee\/UCM336236.pdf(last accessed on October 23 2013)."},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/diaclin.28.1.5"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.48.9.1794"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2010.511"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.4158\/EP.14.6.782"},{"key":"e_1_2_11_19_1","unstructured":"GremplerR ThomasL EckhardtM HimmelsbachF SauerA MarkM EickelmannP.In vitroproperties andIn vivoeffect on urinary glucose excretion of BI 10773 a novel selective SGLT2 inhibitor. 69th Annual Meeting of the American Diabetes Association New Orleans Louisiana 2009. 521 p."},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270009352185"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01462.x"},{"key":"e_1_2_11_22_1","unstructured":"Available at:http:\/\/www.kissei.co.jp\/e_contents\/relation\/2009\/20090703.html(last accessed on October 23 2013)."},{"key":"e_1_2_11_23_1","first-page":"574","article-title":"Effects of AVE2268, a substituted glycopyranoside, on urinary glucose excretion and blood glucose in mice and rats","volume":"58","author":"Bickel M","year":"2008","journal-title":"Arzneimittelforschung"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2008.12.031"},{"key":"e_1_2_11_25_1","unstructured":"Available at:http:\/\/www.drugbank.ca\/drugs\/DB08907(last accessed on October 23 2013)."},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm100332n"},{"key":"e_1_2_11_27_1","first-page":"979","volume":"73","author":"Elkinson S","year":"2013","journal-title":"Canagliflozin: First global approval drugs"},{"key":"e_1_2_11_28_1","unstructured":"Available at:http:\/\/www.invokanahcp.com\/prescribing\u2010information.pdf(last accessed on October 23 2013)."},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12054"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-013-3039-1"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijcp.12322"},{"key":"e_1_2_11_32_1","unstructured":"ForstT GuthrieR GoldenbergR VijapurkarU YeeJ MeiningerG SteinP.Efficacy and safety of canagliflozin in subjects with type 2 diabetes on metformin and pioglitazone. 4th World congress on controversies to consensus in diabetes obesity and hypertension (CODHy) Barcelona Spain 2012. 64 p."},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-2491"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60683-2"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3810\/hp.2013.04.1020"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12090"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2013.05.007"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-1926"},{"key":"e_1_2_11_39_1","unstructured":"Available at:http:\/\/www.invokanahcp.com\/prescribing\u2010information.pdf(last accessed on October 23 2013)."},{"key":"e_1_2_11_40_1","unstructured":"Available at:http:\/\/www.investor.jnj.com\/releasedetail.cfm?ReleaseID=792032(last accessed on October 23 2013)."},{"key":"e_1_2_11_41_1","unstructured":"Available at:http:\/\/www.accessdata.fda.gov\/Scripts\/cder\/ob\/docs\/tempai.cfm(last accessed on October 23 2013)."},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/PHAR.1010"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm701272q"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-1863"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-013-0104-3"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01359.x"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc10-0612"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60407-2"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-0517"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60216-5"},{"key":"e_1_2_11_51_1","first-page":"128","article-title":"Dapagliflozin. lowering blood glucose levels by increasing glucosuria","volume":"36","author":"Hinneburg I","year":"2013","journal-title":"Med Monatsschr Pharm"},{"key":"e_1_2_11_52_1","unstructured":"Available at:http:\/\/www.astrazeneca.com\/Media\/Press\u2010releases\/Article\/20121114\u2010forxiga\u2010eu\u2010approval\u2010type\u20102\u2010diabetes(last accessed on October 23 2013)."},{"key":"e_1_2_11_53_1","unstructured":"Available at:http:\/\/news.bms.com\/press\u2010release\/rd\u2010news\/us\u2010fda\u2010acknowledges\u2010receipt\u2010resubmission\u2010new\u2010drug\u2010application\u2010investigational\u2010(last accessed on October 23 2013)."},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01517.x"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.DMPK-12-RG-082"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(13)70084-6"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-2673"},{"key":"e_1_2_11_58_1","unstructured":"Available at:http:\/\/newsroom.lilly.com\/releasedetail.cfm?releaseid=751101(last accessed on October 23 2013)."},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-011-0713-z"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03256922"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.04.003"},{"key":"e_1_2_11_62_1","unstructured":"Available at:http:\/\/scibite.com\/site\/topic\/DRUG:SCB9x68156(last accessed on October 23 2013)."},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.3109\/07435800.2012.746364"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.112.191593"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm300884k"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm901893x"},{"key":"e_1_2_11_67_1","unstructured":"SeinoY SasakiT FukatsuA SamukawaY SakaiS WatanabeT.A novel potent and highly selective renal sodium glucose co\u2010transporter 2 (SGLT2) inhibitor TS\u2010071 improves glycaemic control and lowers body weight in Japanese patients with type 2 diabetes mellitus. European Association for the Study of Diabetes (EASD). 47th Annual Meeting. Lisbon Portugal2011. Presentation no.148."},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm8013019"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2012.58"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.4155\/cli.10.12"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.112.197426"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.112.049551"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1039\/c2md20163a"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcjd.2012.07.406"},{"key":"e_1_2_11_75_1","first-page":"1499","article-title":"Design, synthesis and in vivo hypoglycemic activity of tetrazole\u2010bearing N\u2010glycosides as SGLT2 inhibitors","volume":"49","author":"Gao YL","year":"2010","journal-title":"Ind J Chem B"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543770903337828"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.04010609"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010030246"}],"container-title":["Medicinal Research Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmed.21314","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmed.21314","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/med.21314","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T12:37:37Z","timestamp":1696595857000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/med.21314"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3,14]]},"references-count":77,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2014,11]]}},"alternative-id":["10.1002\/med.21314"],"URL":"https:\/\/doi.org\/10.1002\/med.21314","archive":["Portico"],"relation":{},"ISSN":["0198-6325","1098-1128"],"issn-type":[{"value":"0198-6325","type":"print"},{"value":"1098-1128","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3,14]]}}}