Diabetes Center, Children and Youth Hospital Auf der Bult, Hannover Medical School, Hannover, Germany.
Department of Medicine, University of California San Diego, San Diego, California.
Diabetes Technol Ther. 2019 Sep;21(9):471-477. doi: 10.1089/dia.2019.0157.
Hypoglycemia rates usually increase when insulin treatment is intensified to improve glycemic control. We evaluated (post hoc) hypoglycemic rates in adult patients with type 1 diabetes (T1D) on sotagliflozin (a dual sodium-glucose cotransporter [SGLT] 1 and 2 inhibitor) in two phase 3, 52-week clinical trials (inTandem 1 and 2; NCT02384941 and NCT02421510). We analyzed rates of documented hypoglycemia (level 1, blood glucose ≥54 to <70 mg/dL) and clinically important hypoglycemia (level 2, glucose <54 mg/dL) in a patient-level pooled analysis ( = 1362) using a negative binomial model adjusted for hemoglobin A1c (HbA1c) at 52 weeks in patients receiving placebo, sotagliflozin 200 mg, and sotagliflozin 400 mg. Rates of level 1 hypoglycemia events per patient-year were 58.25 (95% confidence interval: 50.26-67.50) with placebo, 44.86 (38.83-51.82; = 0.0138 vs. placebo) with sotagliflozin 200 mg, and 45.68 (39.52-52.81; = 0.0220) with sotagliflozin 400 mg. Sotagliflozin was also associated with lower rates of level 2 hypoglycemia: 15.95 (14.37-17.70), 11.51 (10.39-12.76; < 0.0001), and 11.13 (10.03-12.35; < 0.0001) for placebo and sotagliflozin 200 and 400 mg, respectively. The difference in rates of hypoglycemia with sotagliflozin versus placebo became more pronounced as HbA1c decreased. At week 52, level 1 and 2 hypoglycemia events were 22% to 30% less frequent with sotagliflozin added to optimized insulin therapy versus placebo in adults with T1D at any HbA1c level, with greater differences at lower HbA1c values. These findings support the use of sotagliflozin as an insulin adjunct in T1D.
当胰岛素治疗强化以改善血糖控制时，低血糖发生率通常会增加。我们在两项为期 52 周的 3 期临床试验（inTandem1 和 2；NCT02384941 和 NCT02421510）中对接受索格列净（一种双重钠-葡萄糖协同转运蛋白 [SGLT]1 和 2 抑制剂）治疗的 1 型糖尿病（T1D）成年患者（ = 1362）进行了（事后）低血糖发生率评估。我们使用负二项式模型对接受安慰剂、索格列净 200mg 和索格列净 400mg 的患者在 52 周时的血红蛋白 A1c（HbA1c）进行调整，对患者水平的汇总分析（ = 1362）中记录的低血糖（1 级，血糖≥54 至<70mg/dL）和临床重要的低血糖（2 级，血糖<54mg/dL）发生率进行了分析。在接受安慰剂、索格列净 200mg 和索格列净 400mg 的患者中，1 级低血糖事件发生率/患者年分别为 58.25（95%置信区间：50.26-67.50）、44.86（38.83-51.82； = 0.0138 与安慰剂相比）和 45.68（39.52-52.81； = 0.0220）。索格列净还与较低的 2 级低血糖发生率相关：15.95（14.37-17.70）、11.51（10.39-12.76； < 0.0001）和 11.13（10.03-12.35； < 0.0001），分别为安慰剂和索格列净 200mg 和 400mg。随着 HbA1c 的降低，索格列净与安慰剂相比，低血糖发生率的差异变得更加明显。在任何 HbA1c 水平下，与安慰剂相比，在接受优化胰岛素治疗的基础上加用索格列净，1 型糖尿病患者的 1 级和 2 级低血糖事件减少了 22%至 30%，在较低的 HbA1c 值时差异更大。这些发现支持将索格列净作为 1 型糖尿病的胰岛素辅助药物使用。
