Abstract：
YG1699 is a novel inhibitor of sodium-glucose cotransporter 1 (SGLT1) and SGLT2. This double-blind, 3-way crossover trial compared YG1699 to dapagliflozin as an adjunct to insulin in people with type 1 diabetes (T1D) on insulin pump therapy. Treatment periods included four mixed meal tolerance tests (MMTTs) and insulin withdrawal tests per person. Nineteen adults with T1D were randomized to YG1699 10 mg, YG1699 25 mg, and dapagliflozin 10 mg once daily for 1 week in different orders. The primary end point was the difference in area under the curve (AUC) in plasma glucose (AUC0-120min) after an MMTT between treatment groups. Mean change in plasma glucose after an MMTT (AUC0-120min) was lower for YG1699 10 mg vs. dapagliflozin (89.51% of baseline vs. 102.13%, 90% confidence interval (CI) vs. dapagliflozin, -6% to -16%, P = 0.0003) and for YG1699 25 mg (84.83% vs. 102.13%, 90% CI vs. dapagliflozin -13% to -22%, P < 0.0001). At 120 minutes, mean glucose values on no treatment, dapagliflozin, YG1699 10 mg, and YG1699 25 mg were 149 (SE 7.6), 141 (SE 6.1), 128 (SE 6.9), and 115 (SE 7.8) mg/dL, respectively. Insulin dose requirements were lower for YG1699 10 mg and 25 mg vs. dapagliflozin for bolus insulin, and for YG1699 10 mg vs. dapagliflozin for total daily insulin. Safety profiles were similar between treatment groups. YG1699 reduced post-prandial glucose more than dapagliflozin in people with T1D on insulin pump therapy. The results were consistent with dual SGLT1/SGLT2 inhibition by YG1699.
摘要：
YG1699是钠-葡萄糖协同转运蛋白1(SGLT1)和SGLT2的新型抑制剂。这个双盲,3向交叉试验比较了YG1699和达格列净作为胰岛素辅助1型糖尿病患者（T1D）胰岛素泵治疗的胰岛素。治疗期包括每人四次混合餐耐受性测试（MMTT）和胰岛素戒断测试。19名患有T1D的成年人被随机分为YG169910mg，YG169925毫克，和达格列净10毫克，每天一次，持续1周，以不同的顺序。主要终点是治疗组之间的MMTT后血浆葡萄糖(AUC0-120min)的曲线下面积(AUC)的差异。YG169910mg与MMTT（AUC0-120分钟）后血浆葡萄糖的平均变化较低达格列净(基线的89.51%与102.13%，90%置信区间(CI)与dapagliflozin,-6%至-16%，P=0.0003）和YG169925mg（84.83%vs.102.13%，90%CI与达格列净-13%至-22%，P<0.0001)。120分钟时,不治疗时的平均葡萄糖值，dapagliflozin,YG169910mg,YG169925mg为149（SE7.6），141（SE6.1），128（SE6.9），和115（SE7.8）mg/dL，分别。YG169910mg和25mg的胰岛素剂量要求较低。dapagliflozin用于推注胰岛素，和YG169910mgvs.dapagliflozin用于每日总胰岛素。治疗组之间的安全性相似。在胰岛素泵治疗的T1D患者中，YG1699比达格列净更能降低餐后葡萄糖。结果与YG1699的双重SGLT1/SGLT2抑制一致。
