Center for Diabetes Technology, University of Virginia, Charlottesville, Virginia, USA.
Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA.
Diabetes Technol Ther. 2022 Jul;24(7):461-470. doi: 10.1089/dia.2021.0542. Epub 2022 Mar 14.
Use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as adjunct therapy to insulin in type 1 diabetes (T1D) has been previously studied. In this study, we present data from the first free-living trial combining low-dose SGLT2i with commercial automated insulin delivery (AID) or predictive low glucose suspend (PLGS) systems. In an 8-week, randomized, controlled crossover trial, adults with T1D received 5 mg/day empagliflozin (EMPA) or no drug (NOEMPA) as adjunct to insulin therapy. Participants were also randomized to sequential orders of AID (Control-IQ) and PLGS (Basal-IQ) systems for 4 and 2 weeks, respectively. The primary endpoint was percent time-in-range (TIR) 70-180 mg/dL during daytime (7:00-23:00 h) while on AID (NCT04201496). A total of 39 subjects were enrolled, 35 were randomized, 34 (EMPA; = 18 and NOEMPA = 16) were analyzed according to the intention-to-treat principle, and 32 (EMPA; = 16 and NOEMPA = 16) completed the trial. On AID, EMPA versus NOEMPA had higher daytime TIR 81% versus 71% with a mean estimated difference of +9.9% (confidence interval [95% CI] 0.6-19.1); = 0.04. On PLGS, the EMPA versus NOEMPA daytime TIR was 80% versus 63%, mean estimated difference of +16.5% (95% CI 7.3-25.7); < 0.001. One subject on SGLT2i and AID had one episode of diabetic ketoacidosis with nonfunctioning insulin pump infusion site occlusion contributory. In an 8-week outpatient study, addition of 5 mg daily empagliflozin to commercially available AID or PLGS systems significantly improved daytime glucose control in individuals with T1D, without increased hypoglycemia risk. However, the risk of ketosis and ketoacidosis remains. Therefore, future studies with SGLT2i will need modifications to closed-loop control algorithms to enhance safety.
在 1 型糖尿病 (T1D) 中，将钠-葡萄糖共转运蛋白 2 抑制剂 (SGLT2i) 用作胰岛素的辅助治疗已得到先前研究的证实。在这项研究中，我们展示了首个将低剂量 SGLT2i 与商业自动化胰岛素输送 (AID) 或预测性低血糖暂停 (PLGS) 系统相结合的自由生活试验的数据。在一项为期 8 周、随机、对照交叉试验中，T1D 成人接受 5mg/天的恩格列净 (EMPA) 或无药物 (NOEMPA) 作为胰岛素治疗的辅助治疗。参与者还随机接受 AID (Control-IQ) 和 PLGS (Basal-IQ) 系统的顺序治疗，分别为 4 周和 2 周。主要终点是在 AID 期间白天 (7:00-23:00h) 70-180mg/dL 的时间百分比 (TIR) (NCT04201496)。共有 39 名受试者入组，35 名随机分组，34 名 (EMPA; = 18 名，NOEMPA; = 16 名) 根据意向治疗原则进行分析，32 名 (EMPA; = 16 名，NOEMPA; = 16 名) 完成了试验。在 AID 上，与无药物组相比，恩格列净组白天 TIR 为 81%，而 71%，平均估计差异为+9.9% (置信区间 [95% CI] 0.6-19.1); = 0.04。在 PLGS 上，与无药物组相比，恩格列净组白天 TIR 为 80%，而 63%，平均估计差异为+16.5% (95% CI 7.3-25.7); < 0.001。一名接受 SGLT2i 和 AID 治疗的受试者发生了一次糖尿病酮症酸中毒，原因是胰岛素泵输注部位堵塞导致胰岛素泵无法正常工作。在一项为期 8 周的门诊研究中，在商业上可获得的 AID 或 PLGS 系统中每天添加 5mg 恩格列净显著改善了 T1D 个体的白天血糖控制，而低血糖风险没有增加。然而，酮症和酮症酸中毒的风险仍然存在。因此，未来的 SGLT2i 研究需要对闭环控制算法进行修改，以提高安全性。
