{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:32:20Z","timestamp":1780572740965,"version":"3.54.1"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,12,18]],"date-time":"2017-12-18T00:00:00Z","timestamp":1513555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sodium glucose cotransporter 2 inhibitors increase urinary glucose excretion (UGE) by lowering the renal threshold for glucose (RT<jats:sub>G<\/jats:sub>). We aimed to quantify the effect of the sodium glucose cotransporter inhibitor empagliflozin on renal glucose reabsorption in patients with type 1 diabetes mellitus (T1DM) using a mechanistic population pharmacokinetic\u2013pharmacodynamic (PK\u2010PD) model and to compare results with analyses in patients with type 2 diabetes mellitus (T2DM). The PK\u2010PD model was developed using data from a randomized phase 2 study in which patients with T1DM received oral once\u2010daily empagliflozin 2.5 mg, empagliflozin 10 mg, empagliflozin 25 mg, or placebo as an adjunct to insulin. The model assumed that UGE was dependent on plasma glucose and renal function and that empagliflozin lowered RT<jats:sub>G<\/jats:sub>. The final model was evaluated using visual predictive checks and found to be consistent with observed data. Calculated RT<jats:sub>G<\/jats:sub> with placebo was 181 mg\/dL, and with empagliflozin (steady state) 1 mg and 2.5 mg was 53.4 mg\/dL and 12.5 mg\/dL, respectively. Empagliflozin 10 mg and 25 mg yielded negative RT<jats:sub>G<\/jats:sub> values, implying RT<jats:sub>G<\/jats:sub> was reduced to a negligible value. Although estimated PK\u2010PD parameters were generally comparable between patients with T1DM and patients with T2DM, slight differences were evident, leading to lower RT<jats:sub>G<\/jats:sub> and higher UGE in patients with T1DM compared with patients with T2DM. In conclusion, the model provided a reasonable description of UGE in response to administration of empagliflozin and placebo in patients with T1DM.<\/jats:p>","DOI":"10.1002\/jcph.1051","type":"journal-article","created":{"date-parts":[[2017,12,18]],"date-time":"2017-12-18T16:17:03Z","timestamp":1513613823000},"page":"640-649","source":"Crossref","is-referenced-by-count":11,"title":["Population Pharmacokinetic\u2013 Pharmacodynamic Analysis to Characterize the Effect of Empagliflozin on Renal Glucose Threshold in Patients With Type 1 Diabetes Mellitus"],"prefix":"10.1002","volume":"58","author":[{"given":"John","family":"Mondick","sequence":"first","affiliation":[{"name":"Metrum Research Group  Tariffville CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Riggs","sequence":"additional","affiliation":[{"name":"Metrum Research Group  Tariffville CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kaspers","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; 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