OBJECTIVE Inhibiting sodium–glucose cotransporters (SGLTs) improves glycemic and cardiovascular outcomes in patients with type 2 diabetes (T2D). We investigated the differential impact of selective SGLT2 inhibition and dual inhibition of SGLT1 and SGLT2 on multiple parameters. RESEARCH DESIGN AND METHODS Using a double-blind, parallel-group design, we randomized 40 patients with T2D and hypertension to receive the dual SGLT1 and SGLT2 inhibitor sotagliflozin 400 mg or the selective SGLT2 inhibitor empagliflozin 25 mg, with preexisting antihypertensive treatment, for 8 weeks. In an in-house testing site, mixed-meal tolerance tests (MMTTs) and other laboratory and clinical evaluations were used to study metabolic, intestinal, cardiovascular, and urinary parameters over 24 h. RESULTS Changes from baseline in glycemic and blood pressure control; intestinal, urine, and metabolic parameters; and cardiovascular biomarkers were generally similar with sotagliflozin and empagliflozin. During the breakfast MMTT, sotagliflozin significantly reduced incremental area under the curve (AUC) values for postprandial glucose, insulin, and glucose-dependent insulinotropic polypeptide (GIP) and significantly increased incremental AUCs for postprandial glucagon-like peptide 1 (GLP-1) relative to empagliflozin, consistent with sotagliflozin-mediated inhibition of intestinal SGLT1. These changes waned during lunch and dinner MMTTs. Both treatments significantly lowered GIP incremental AUCs relative to baseline over the 14 h MMTT interval; the most vigorous effect was seen with sotagliflozin soon after start of the first meal of the day. No serious or severe adverse events were observed. CONCLUSIONS Changes from baseline in glycemic and blood pressure control, cardiovascular biomarkers, and other parameters were comparable between sotagliflozin and empagliflozin. However, sotagliflozin but not empagliflozin inhibited intestinal SGLT1 after breakfast as shown by larger changes in postprandial glucose, insulin, GIP, and GLP-1 AUCs, particularly after breakfast. Additional study is warranted to assess the clinical relevance of transient SGLT1 inhibition and differences in incretin responses (NCT03462069).

中文翻译：

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Sotagliflozin 与 Empagliflozin 相比对 2 型糖尿病患者的代谢、肠道和心血管影响：一项随机、双盲研究

目的 抑制钠-葡萄糖协同转运蛋白 (SGLT) 可改善 2 型糖尿病 (T2D) 患者的血糖和心血管结局。我们研究了选择性 SGLT2 抑制和 SGLT1 和 SGLT2 双重抑制对多个参数的不同影响。研究设周。在内部测试站点，混合膳食耐受测试 (MMTT) 和其他实验室和临床评估用于研究 24 小时内的代谢、肠道、心血管和泌尿参数。结果血糖和血压控制的基线变化；肠道、尿液和代谢参数；和心血管生物标志物与 sotagliflozin 和 empagliflozin 大致相似。在早餐 MMTT 期间，sotagliflozin 显着降低餐后葡萄糖、胰岛素和葡萄糖依赖性促胰岛素多肽 (GIP) 的增量曲线下面积 (AUC) 值，并显着增加餐后胰高血糖素样肽 1 (GLP-1) 相对曲线下的增量 AUC与 empagliflozin 一致，与 sotagliflozin 介导的肠道 SGLT1 抑制一致。这些变化在午餐和晚餐 MMTT 期间减弱。两种治疗均显着降低了 14 小时 MMTT 间隔内相对于基线的 GIP 增量 AUC；在一天的第一餐开始后不久，使用 sotagliflozin 就可以看到最强烈的效果。没有观察到严重或严重的不良事件。结论：sotagliflozin 和 empagliflozin 的血糖和血压控制、心血管生物标志物和其他参数相对于基线的变化具有可比性。然而，sotagliflozin 而不是 empagliflozin 在早餐后抑制肠道 SGLT1，如餐后葡萄糖、胰岛素、GIP 和 GLP-1 AUC 的较大变化所示，尤其是早餐后。需要进一步的研究来评估瞬时 SGLT1 抑制的临床相关性和肠促胰岛素反应的差异 (NCT03462069)。尤其是早餐后。需要进一步的研究来评估瞬时 SGLT1 抑制的临床相关性和肠促胰岛素反应的差异 (NCT03462069)。尤其是早餐后。需要进一步的研究来评估瞬时 SGLT1 抑制的临床相关性和肠促胰岛素反应的差异 (NCT03462069)。