{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T18:07:51Z","timestamp":1776535671628,"version":"3.51.2"},"reference-count":24,"publisher":"American Diabetes Association","issue":"5","license":[{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"vor","delay-in-days":3059,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,5,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>Ipragliflozin, a sodium-glucose cotransporter 2 inhibitor, stimulates glycosuria and lowers glycemia in patients with type 2 diabetes (T2DM). The objective of this study was to assess the pharmacodynamics of ipragliflozin in T2DM patients with impaired renal function.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>Glycosuria was measured before and after a single ipragliflozin dose in 8 nondiabetic subjects and 57 T2DM patients (age 62 \u00b1 9 years, fasting glucose 133 \u00b1 39 mg\/dL, mean \u00b1 SD) with normal renal function (assessed as the estimated glomerular filtration rate [eGFR]) (eGFR1 \u226590 mL \u00b7 min\u20131 \u00b7 1.73 m\u22122), mild (eGFR2 \u226560 to &amp;lt;90), moderate (eGFR3 \u226530 to &amp;lt;60), or severe reduction in eGFR (eGFR4 \u226415 to &amp;lt;30).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Ipragliflozin significantly increased urinary glucose excretion in each eGFR class (P &amp;lt; 0.0001). However, ipragliflozin-induced glycosuria declined (median [IQR]) across eGFR class (from 46 mg\/min [33] in eGFR1 to 8 mg\/min [7] in eGFR4, P &amp;lt; 0.001). Ipragliflozin-induced fractional glucose excretion (excretion\/filtration) was 39% [27] in the T2DM patients (pooled data), similar to that of the nondiabetic subjects (37% [17], P = ns). In bivariate analysis of the pooled data, ipragliflozin-induced glycosuria was directly related to eGFR and fasting glucose (P &amp;lt; 0.0001 for both, r2 = 0.55), predicting a decrement in 24-h glycosuria of 15 g for each 20 mL\/min decline in eGFR and an increase of 7 g for each 10 mg\/dL increase in glucose above fasting normoglycemia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>In T2DM patients, ipragliflozin increases glycosuria in direct, linear proportion to GFR and degree of hyperglycemia, such that its amount can be reliably predicted in the individual patient. Although absolute glycosuria decreases with declining GFR, the efficiency of ipragliflozin action (fractional glucose excretion) is maintained in patients with severe renal impairment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc12-1503","type":"journal-article","created":{"date-parts":[[2013,1,29]],"date-time":"2013-01-29T11:11:32Z","timestamp":1359457892000},"page":"1260-1265","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":68,"title":["Renal Glucose Handling"],"prefix":"10.2337","volume":"36","author":[{"given":"Ele","family":"Ferrannini","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Pisa School of Medicine, Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan A.","family":"Veltkamp","sequence":"additional","affiliation":[{"name":"Global Clinical Pharmacology & Exploratory Development, Astellas Pharma, Leiderdorp, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald A.","family":"Smulders","sequence":"additional","affiliation":[{"name":"Global Clinical Pharmacology & Exploratory Development, Astellas Pharma, Leiderdorp, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Kadokura","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Astellas Pharma Inc., Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","published-online":{"date-parts":[[2013,4,13]]},"reference":[{"key":"2022031220065721300_B1","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1001\/jama.291.3.335","article-title":"Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes","volume":"291","author":"Saydah","year":"2004","journal-title":"JAMA"},{"key":"2022031220065721300_B2","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nrd3180","article-title":"SGLT2 inhibition\u2014a novel strategy for diabetes treatment","volume":"9","author":"Chao","year":"2010","journal-title":"Nat Rev Drug Discov"},{"key":"2022031220065721300_B3","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1172\/JCI116972","article-title":"The human kidney low affinity Na+\/glucose cotransporter SGLT2. 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