Youngene Therapeutics Co., Ltd., Zhangjiang Hi-Tech Park, Shanghai, China.
Prosciento, Inc., Chula Vista, California, USA.
Clin Pharmacol Ther. 2024 Jun;115(6):1383-1390. doi: 10.1002/cpt.3225. Epub 2024 Mar 8.
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 (AUC) after an MMTT between treatment groups. Mean change in plasma glucose after an MMTT (AUC) 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.
YG1699 是一种新型钠-葡萄糖共转运蛋白 1（SGLT1）和 SGLT2 抑制剂。这项双盲、三交叉试验比较了 YG1699 与达格列净作为胰岛素的辅助治疗，应用于接受胰岛素泵治疗的 1 型糖尿病（T1D）患者。每位患者的治疗期包括四次混合餐耐量试验（MMTT）和胰岛素撤药试验。19 名 T1D 成人随机接受 YG1699 10mg、YG1699 25mg 和达格列净 10mg 每日一次治疗，治疗顺序不同。主要终点是治疗组间 MMTT 后血浆葡萄糖（AUC）曲线下面积（AUC）的差异。与达格列净相比，YG1699 10mg 治疗后 MMTT 时的平均血浆葡萄糖变化（AUC）更低（89.51%基线值比 102.13%，90%置信区间[CI]比达格列净，-6%至-16%，P=0.0003），YG1699 25mg 也更低（84.83%比 102.13%，90%CI 比达格列净，-13%至-22%，P<0.0001）。在 120 分钟时，无治疗、达格列净、YG1699 10mg 和 YG1699 25mg 的平均血糖值分别为 149（SE 7.6）、141（SE 6.1）、128（SE 6.9）和 115（SE 7.8）mg/dL。与达格列净相比，YG1699 10mg 和 25mg 治疗时需要的胰岛素剂量更少，用于追加胰岛素，而 YG1699 10mg 治疗时用于总胰岛素剂量。治疗组之间的安全性特征相似。在接受胰岛素泵治疗的 T1D 患者中，YG1699 降低餐后血糖的作用优于达格列净。结果与 YG1699 双重抑制 SGLT1/SGLT2 一致。
