<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Caroline Simoens</style></author><author><style face="normal" font="default" size="100%">Koenraad Philippaert</style></author><author><style face="normal" font="default" size="100%">Caroline Wuyts</style></author><author><style face="normal" font="default" size="100%">Séverine Goscinny</style></author><author><style face="normal" font="default" size="100%">Els Van Hoeck</style></author><author><style face="normal" font="default" size="100%">Joris Van Loco</style></author><author><style face="normal" font="default" size="100%">Jaak Billen</style></author><author><style face="normal" font="default" size="100%">Jan de Hoon</style></author><author><style face="normal" font="default" size="100%">Els Ampe</style></author><author><style face="normal" font="default" size="100%">Vangoitsenhoven, Roman</style></author><author><style face="normal" font="default" size="100%">Ann Mertens</style></author><author><style face="normal" font="default" size="100%">Rudi Vennekens</style></author><author><style face="normal" font="default" size="100%">Van der Schueren, Bart</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Pharmacokinetics of Oral Rebaudioside A in Patients with Type 2 Diabetes Mellitus and Its Effects on Glucose Homeostasis: A Placebo-Controlled Crossover Trial</style></title><secondary-title><style face="normal" font="default" size="100%">European Journal of Drug Metabolism and Pharmacokinetics</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2022</style></year><pub-dates><date><style  face="normal" font="default" size="100%">Jan-11-2022</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">47</style></volume><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Background and Objectives&lt;/p&gt;

&lt;p&gt;Rebaudioside A, a steviol glycoside, is deglycosylated by intestinal microflora prior to the absorption of steviol and conjugation to steviol glucuronide. While glucose-lowering properties are observed for rebaudioside A in mice, they have been attributed to the metabolites steviol and steviol glucuronide. We aimed to characterize the pharmacokinetic and pharmacodynamic properties of rebaudioside A and its metabolites in patients with early-onset type 2 diabetes mellitus (T2DM).&lt;/p&gt;

&lt;p&gt;Methods&lt;/p&gt;

&lt;p&gt;This randomized, placebo-controlled, open-label, two-way crossover trial was performed in subjects with T2DM on metformin or no therapy at the University Hospitals Leuven, Belgium. Following oral rebaudioside A (3 g), plasma concentrations of rebaudioside A, steviol and steviol glucuronide were determined. The effect on glucose homeostasis was examined by an oral glucose tolerance test (OGTT) performed 19 h following rebaudioside A administration, i.e. the presumed time of maximal steviol and steviol glucuronide concentrations. The primary pharmacodynamic endpoint was the difference in area under the blood glucose concentration–time curve during the first 2 h of the OGTT (AUCGlucose(0–2h)) for rebaudioside A vs. placebo.&lt;/p&gt;

&lt;p&gt;Results&lt;/p&gt;

&lt;p&gt;In total, 30 subjects [63.5 (57.8–69.0) years&amp;nbsp;of age, 86.7% male] completed the trial. Rebaudioside A was detected as early as 1 h after administration in nearly all subjects. As expected, steviol and steviol glucuronide reached their maximal concentrations at 19.5 h following rebaudioside A administration. Rebaudioside A did not lower the AUCGlucose(0–2h)&amp;nbsp;compared to placebo (−&amp;nbsp;0.7 (95% CI −&amp;nbsp;22.3; 20.9) h·mg/dL,&amp;nbsp;P&amp;nbsp;= 0.95). Insulin and C-peptide concentrations were also comparable between both conditions (P&amp;nbsp;&amp;gt; 0.05).&lt;/p&gt;

&lt;p&gt;Conclusion&lt;/p&gt;

&lt;p&gt;Rebaudioside A is readily absorbed after oral administration and metabolized to steviol and steviol glucuronide. However, no effect on glucose nor insulin or C-peptide excursion was observed during the OGTT at the time of maximal metabolite concentrations. Thus, no antidiabetic properties of rebaudioside A could be observed in patients with T2DM after single oral use.&lt;/p&gt;
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