Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
Departments of Medicine and Pediatrics, Barbara Davis Center for Diabetes, University of Colorado Denver, Aurora, CO.
Diabetes Care. 2018 Sep;41(9):1970-1980. doi: 10.2337/dc18-0343. Epub 2018 Jun 24.
Evaluate the efficacy and safety of the dual sodium-glucose cotransporter 1 (SGLT1) and SGLT2 inhibitor sotagliflozin in combination with optimized insulin in type 1 diabetes (T1D).
The inTandem1 trial, a double-blind, 52-week phase 3 trial, randomized North American adults with T1D to placebo ( = 268), sotagliflozin 200 mg ( = 263), or sotagliflozin 400 mg ( = 262) after 6 weeks of insulin optimization. The primary end point was HbA change from baseline at 24 weeks. HbA, weight, and safety were also assessed through 52 weeks.
From a mean baseline of 7.57%, placebo-adjusted HbA reductions were 0.36% and 0.41% with sotagliflozin 200 and 400 mg, respectively, at 24 weeks and 0.25% and 0.31% at 52 weeks (all < 0.001). Among patients with a baseline HbA ≥7.0%, an HbA <7% was achieved by 15.7%, 27.2%, and 40.3% of patients receiving placebo, sotagliflozin 200 mg, and sotagliflozin 400 mg, respectively ( ≤ 0.003 vs. placebo) at 24 weeks. At 52 weeks, mean treatment differences between sotagliflozin 400 mg and placebo were -1.08 mmol/L for fasting plasma glucose, -4.32 kg for weight, and -15.63% for bolus insulin dose and -11.87% for basal insulin dose (all < 0.001). Diabetes Treatment Satisfaction Questionnaire scores increased significantly by 2.5 points with sotagliflozin versus placebo ( < 0.001) at 24 weeks. Genital mycotic infections and diarrhea occurred more frequently with sotagliflozin. Adjudicated diabetic ketoacidosis (DKA) occurred in 9 (3.4%) and 11 (4.2%) patients receiving sotagliflozin 200 and 400 mg, respectively, and in 1 (0.4%) receiving placebo. Severe hypoglycemia occurred in 17 (6.5%) patients from each sotagliflozin group and 26 (9.7%) patients receiving placebo.
In a 1-year T1D study, sotagliflozin combined with optimized insulin therapy was associated with sustained HbA reduction, weight loss, lower insulin dose, fewer episodes of severe hypoglycemia, improved patient-reported outcomes, and more DKA relative to placebo (ClinicalTrials.gov, NCT02384941).
评估双重钠-葡萄糖协同转运蛋白 1（SGLT1）和 SGLT2 抑制剂索格列净联合优化胰岛素治疗 1 型糖尿病（T1D）的疗效和安全性。
在一项为期 52 周的双盲、3 期 inTandem1 试验中，北美成年 T1D 患者在胰岛素优化 6 周后，随机分为安慰剂（ = 268）、索格列净 200mg（ = 263）或索格列净 400mg（ = 262）组。主要终点是 24 周时与基线相比的 HbA 变化。通过 52 周评估 HbA、体重和安全性。
从平均基线 7.57%开始，安慰剂校正的 HbA 降低分别为索格列净 200mg 和 400mg 组的 0.36%和 0.41%，在 24 周时为 0.25%和 0.31%，在 52 周时（均 < 0.001）。在基线 HbA≥7.0%的患者中，接受安慰剂、索格列净 200mg 和索格列净 400mg 治疗的患者分别有 15.7%、27.2%和 40.3%在 24 周时达到 HbA<7%（均 ≤ 0.003 与安慰剂相比）。在 52 周时，索格列净 400mg 与安慰剂相比，空腹血糖的平均治疗差异为-1.08mmol/L，体重降低-4.32kg，胰岛素冲击剂量降低-15.63%，基础胰岛素剂量降低-11.87%（均 < 0.001）。与安慰剂相比，索格列净治疗组糖尿病治疗满意度问卷评分在 24 周时显著增加了 2.5 分（ < 0.001）。索格列净治疗组更常发生生殖器真菌感染和腹泻。接受索格列净 200mg 和 400mg 治疗的患者分别有 9（3.4%）和 11（4.2%）例发生糖尿病酮症酸中毒（DKA），而接受安慰剂治疗的患者有 1 例（0.4%）发生。接受索格列净治疗的患者分别有 17（6.5%）和 17（6.5%）例发生严重低血糖，而接受安慰剂治疗的患者有 26（9.7%）例发生严重低血糖。
在一项为期 1 年的 T1D 研究中，与安慰剂相比，索格列净联合优化胰岛素治疗可持续降低 HbA、体重、降低胰岛素剂量、减少严重低血糖发作、改善患者报告结局，并增加 DKA（临床试验.gov，NCT02384941）。
