索格列净联合胰岛素治疗 1 型糖尿病的疗效。
Effects of Sotagliflozin Added to Insulin in Patients with Type 1 Diabetes.
机构信息
From the University of Colorado Denver, Aurora (S.K.G.); the University of California at San Diego, San Diego (R.R.H.); Lexicon Pharmaceuticals, The Woodlands (P.B., D.G.-P., P.L., P.S.), the University of Texas Southwestern Medical Center, Dallas (D.K.M.), and Baylor College of Medicine and Texas Children's Hospital, Houston (J.A.K.) - all in Texas; the Diabetes Research Center, University of North Carolina School of Medicine, Durham (J.B.B.); the University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, United Kingdom (M.J.D.); the University of Sydney, Sydney (G.R.F.); University Campus Bio-Medico of Rome, Rome (P.P.); Vall d'Hebron Research Institute, Barcelona, and CIBERDEM-Instituto de Salud Carlos III, Madrid (R.S.); Diabetes Center Auf der Bult, Hannover Medical School, Hannover, Germany (T.D.); and the University of Southern California, Los Angeles (A.P.).
出版信息
N Engl J Med. 2017 Dec 14;377(24):2337-2348. doi: 10.1056/NEJMoa1708337. Epub 2017 Sep 13.
BACKGROUND
In most patients with type 1 diabetes, adequate glycemic control is not achieved with insulin therapy alone. We evaluated the safety and efficacy of sotagliflozin, an oral inhibitor of sodium-glucose cotransporters 1 and 2, in combination with insulin treatment in patients with type 1 diabetes.
METHODS
In this phase 3, double-blind trial, which was conducted at 133 centers worldwide, we randomly assigned 1402 patients with type 1 diabetes who were receiving treatment with any insulin therapy (pump or injections) to receive sotagliflozin (400 mg per day) or placebo for 24 weeks. The primary end point was a glycated hemoglobin level lower than 7.0% at week 24, with no episodes of severe hypoglycemia or diabetic ketoacidosis after randomization. Secondary end points included the change from baseline in glycated hemoglobin level, weight, systolic blood pressure, and mean daily bolus dose of insulin.
RESULTS
A significantly larger proportion of patients in the sotagliflozin group than in the placebo group achieved the primary end point (200 of 699 patients [28.6%] vs. 107 of 703 [15.2%], P<0.001). The least-squares mean change from baseline was significantly greater in the sotagliflozin group than in the placebo group for glycated hemoglobin (difference, -0.46 percentage points), weight (-2.98 kg), systolic blood pressure (-3.5 mm Hg), and mean daily bolus dose of insulin (-2.8 units per day) (P≤0.002 for all comparisons). The rate of severe hypoglycemia was similar in the sotagliflozin group and the placebo group (3.0% [21 patients] and 2.4% [17], respectively). The rate of documented hypoglycemia with a blood glucose level of 55 mg per deciliter (3.1 mmol per liter) or below was significantly lower in the sotagliflozin group than in the placebo group. The rate of diabetic ketoacidosis was higher in the sotagliflozin group than in the placebo group (3.0% [21 patients] and 0.6% [4], respectively).
CONCLUSIONS
Among patients with type 1 diabetes who were receiving insulin, the proportion of patients who achieved a glycated hemoglobin level lower than 7.0% with no severe hypoglycemia or diabetic ketoacidosis was larger in the group that received sotagliflozin than in the placebo group. However, the rate of diabetic ketoacidosis was higher in the sotagliflozin group. (Funded by Lexicon Pharmaceuticals; inTandem3 ClinicalTrials.gov number, NCT02531035 .).
背景
在大多数 1 型糖尿病患者中，单独使用胰岛素治疗无法达到足够的血糖控制。我们评估了钠-葡萄糖共转运蛋白 1 和 2 的口服抑制剂索格列净联合胰岛素治疗 1 型糖尿病患者的安全性和疗效。
方法
在这项在全球 133 个中心进行的 3 期、双盲试验中，我们将 1402 名正在接受任何胰岛素治疗（泵或注射）的 1 型糖尿病患者随机分配，接受索格列净（每天 400mg）或安慰剂治疗 24 周。主要终点是在随机分组后无严重低血糖或糖尿病酮症酸中毒的情况下，24 周时糖化血红蛋白水平低于 7.0%。次要终点包括从基线开始的糖化血红蛋白水平、体重、收缩压和平均每日胰岛素推注剂量的变化。
结果
索格列净组达到主要终点的患者比例明显高于安慰剂组（200/699 例 [28.6%] vs. 107/703 例 [15.2%]，P<0.001）。索格列净组的糖化血红蛋白（差值 -0.46 个百分点）、体重（-2.98kg）、收缩压（-3.5mmHg）和平均每日胰岛素推注剂量（-2.8 单位/天）的变化均明显大于安慰剂组（所有比较 P≤0.002）。索格列净组和安慰剂组的严重低血糖发生率相似（分别为 3.0%[21 例]和 2.4%[17 例]）。索格列净组血糖水平为 55mg/dL（3.1mmol/L）或以下的有记录低血糖发生率明显低于安慰剂组。索格列净组糖尿病酮症酸中毒发生率高于安慰剂组（分别为 3.0%[21 例]和 0.6%[4 例]）。
结论
在接受胰岛素治疗的 1 型糖尿病患者中，索格列净组糖化血红蛋白水平低于 7.0%且无严重低血糖或糖尿病酮症酸中毒的患者比例高于安慰剂组。然而，索格列净组糖尿病酮症酸中毒的发生率更高。（由 Lexicon Pharmaceuticals 资助；inTandem3 ClinicalTrials.gov 编号，NCT02531035）。
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