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Greater A1C reductions were produced by the 400 mg once a day dose than the 200 mg once a day dose without higher urinary glucose excretion.
SGLT2 is responsible for most glucose reabsorption in the kidney, so inhibition boosts urinary glucose excretion.
EST Location: Orange County Convention Center, Orlando, Florida Titles: -- In Vitro and In Vivo Pharmacological Properties of ASP1941, a Novel, Potent and Selective SGLT2 Inhibitor (Poster # 570-P) -- ASP1941, a Novel, Potent and Selective SGLT2 Inhibitor, Improves Hemoglobin A1c and Symptoms of Diabetes in Animal Models (Poster # 562-P) -- ASP1941, a Novel and Selective SGLT2 Inhibitor, Stimulates Urinary Glucose Excretion in Healthy Subjects (Poster # 565-P) -- ASP1941, a Novel and Selective Inhibitor of Sodium- Glucose Co-Transporter 2 (SGLT2), Reduces Fasting Plasma Glucose in Type 2 Diabetes Mellitus Patients Over 28 Days (Poster # 566-P)
Canagliflozin lowers postprandial plasma glucose and insulin excursions by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion (Abstract 244; results from the Phase I study DIA1022)
About the Clinical Trial The mechanistic study was designed to assess pharmacodynamic parameters, including postprandial glucose (PPG), insulin, total and active GLP-1, PYY, and urinary glucose excretion (UGE).
Pharmacodynamic effects, include urinary glucose excretion, fasting plasma glucose, insulin, PYY and GLP-1 (total and active) were assessed at multiple time points during the 12-day dosing period.
In preclinical studies, animals treated with LX4211 demonstrated increased urinary glucose excretion and decreased blood HbA1c levels (a marker of long-term blood sugar levels).
Consistent with the mechanism of action of LX4211, there was also a significant, dose-dependent increase in 24-hour urinary glucose excretion throughout the study period relative to placebo in both dose groups (p<0.