BACKGROUND This analysis evaluated the efficacy and safety of sotagliflozin, a dual SGLT1&2 inhibitor, added to insulin in patients with type 1 diabetes and chronic kidney disease (CKD). METHODS We used data from the 52-week pooled inTandem1&2 trials and the 24-week inTandem3 trial to assess the effects of sotagliflozin (200mg [inTandem 1&2 only] or 400mg daily) versus placebo on glycated hemoglobin (HbA1c; primary endpoint), body weight, systolic blood pressure (BP), insulin dose, and safety endpoints including adjudicated severe hypoglycemia and diabetic ketoacidosis (DKA), stratified by CKD. RESULTS CKD was identified in 237/1575 of inTandem1&2 participants and 228/1402 of inTandem3 participants. At week-24, significant, placebo-adjusted reductions in HbA1c were observed - inTandem1&2: Non-CKD subgroup (sotagliflozin 200mg: -0.4%, 95% CI -0.4 to -0.3; 400mg: -0.4%, 95% CI -0.5 to -0.3) and CKD subgroup (sotagliflozin 200mg: -0.4%, 95% CI -0.6 to -0.1; 400mg: -0.3%, 95% CI -0.5 to -0.1). For systolic BP, there was a significant reduction at week-24 with sotagliflozin in the non-CKD subgroup but no effect in the CKD subgroup in inTandem1&2. At week-52, the incidence of severe hypoglycemia was lower with sotagliflozin (7% on 200 mg and 4% on 400 mg) compared to placebo (17%) in the CKD subgroup of inTandem1&2, whereas the incidence of severe hypoglycemia was 5-6% across non-CKD subgroups. The incidence of adjudicated DKA at week-52 was 1%, 5%, and 3% for placebo, 200 mg, and 400 mg in the CKD subgroup compared to 0%, 3%, and 4% in the non-CKD subgroup. Results were generally similar in inTandem3 except systolic BP was significantly reduced with sotagliflozin versus placebo in CKD and non-CKD subgroups. CONCLUSIONS In participants with type 1 diabetes and CKD, sotagliflozin treatment had similar HbA1c, body weight, and systolic BP lowering effects as in participants with type 1 diabetes without CKD. Additionaly, sotagliflozin was associated with a lower to neutral risk of severe hypoglycemia and did not significantly increase the risk of DKA among a small number of DKA events.

中文翻译：

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Sotagliflozin 在 1 型糖尿病和 CKD 患者中的疗效和安全性。


背景 该分析评估了 sotagliflozin（一种双重 SGLT1&2 抑制剂）添加到胰岛素中对 1 型糖尿病和慢性肾病 （CKD） 患者的疗效和安全性。方法 我们使用来自 52 周合并的 inTandem1&2 试验和 24 周 inTandem3 试验的数据来评估索格列净（200 毫克 [仅 InTandem 1&2] 或每天 400 毫克）与安慰剂对糖化血红蛋白 （HbA1c;主要终点）、体重、收缩压 （BP）、胰岛素剂量和安全性终点的影响，包括判定的严重低血糖和糖尿病酮症酸中毒 （DKA）， 按 CKD 分层。结果 在 237/1575 的 inTandem1&2 参与者和 228/1402 的 inTandem3 参与者中发现了 CKD。在第 24 周，观察到安慰剂调整后 HbA1c 的显着降低 - inTandem1&2：非 CKD 亚组（索格列净 200 毫克：-0.4%，95% CI -0.4 至 -0.3;400 毫克：-0.4%，95% CI -0.5 至 -0.3）和 CKD 亚组（索格列净 200 毫克：-0.4%，95% CI -0.6 至 -0.1;400 毫克：-0.3%，95% CI -0.5 至 -0.1）。对于收缩压，非 CKD 亚组在第 24 周时索格列净显著降低，但在 inTandem1&2 中 CKD 亚组没有影响。在第 52 周时，在 inTandem1&2 的 CKD 亚组中，索格列净组（200 mg 组为 7%，400 mg 组为 4%）相比，严重低血糖的发生率较低（200 mg 组为 7%，400 mg 组为 4%），而非 CKD 亚组中严重低血糖的发生率为 5-6%。CKD 亚组安慰剂、 200 mg 和 400 mg 在第 52 周时判定的 DKA 发生率为 1% 、 5% 和 3%，而非 CKD 亚组为 0% 、 3% 和 4%。inTandem3 的结果通常相似，但 CKD 和非 CKD 亚组与安慰剂相比，索格列净组的收缩压显著降低。 结论 在 1 型糖尿病合并 CKD 的参与者中，索格列净治疗具有与无 CKD 的 1 型糖尿病参与者相似的 HbA1c 、体重和收缩压降低作用。此外，索格列净与严重低血糖的较低至中性风险相关，并且在少数 DKA 事件中不会显着增加 DKA 的风险。