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索格列净:首个双重 SGLT 抑制剂:当前展望与前景。

Sotagliflozin, the first dual SGLT inhibitor: current outlook and perspectives.

机构信息

Center for Endocrine and Metabolic Diseases, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.

Istituto di Patologia Speciale Medica e Semeiotica Clinica, Università Cattolica del Sacro Cuore, Rome, Italy.

出版信息

Cardiovasc Diabetol. 2019 Feb 28;18(1):20. doi: 10.1186/s12933-019-0828-y.

Abstract

Sotagliflozin is a dual sodium-glucose co-transporter-2 and 1 (SGLT2/1) inhibitor for the treatment of both type 1 (T1D) and type 2 diabetes (T2D). Sotagliflozin inhibits renal sodium-glucose co-transporter 2 (determining significant excretion of glucose in the urine, in the same way as other, already available SGLT-2 selective inhibitors) and intestinal SGLT-1, delaying glucose absorption and therefore reducing post prandial glucose. Well-designed clinical trials, have shown that sotagliflozin (as monotherapy or add-on therapy to other anti-hyperglycemic agents) improves glycated hemoglobin in adults with T2D, with beneficial effects on bodyweight and blood pressure. Similar results have been obtained in adults with T1D treated with either continuous subcutaneous insulin infusion or multiple daily insulin injections, even after insulin optimization. A still ongoing phase 3 study is currently evaluating the effect of sotagliflozin on cardiovascular outcomes (ClinicalTrials.gov NCT03315143). In this review we illustrate the advantages and disadvantages of dual SGLT 2/1 inhibition, in order to better characterize and investigate its mechanisms of action and potentialities.

摘要

索格列净是一种双重钠-葡萄糖共转运蛋白 2 和 1(SGLT2/1)抑制剂,用于治疗 1 型(T1D)和 2 型糖尿病(T2D)。索格列净抑制肾脏钠-葡萄糖共转运蛋白 2(决定葡萄糖在尿液中的大量排泄,与其他已有的 SGLT-2 选择性抑制剂相同)和肠道 SGLT-1,从而延缓葡萄糖吸收,降低餐后血糖。精心设计的临床试验表明,索格列净(作为单药治疗或添加到其他抗高血糖药物治疗)可改善 T2D 成人的糖化血红蛋白,对体重和血压有有益影响。在接受连续皮下胰岛素输注或多次每日胰岛素注射治疗的 T1D 成人中也获得了类似的结果,甚至在胰岛素优化后也是如此。一项仍在进行的 3 期研究目前正在评估索格列净对心血管结局的影响(ClinicalTrials.gov NCT03315143)。在这篇综述中,我们说明了双重 SGLT2/1 抑制的优缺点,以便更好地描述和研究其作用机制和潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b4d/6393994/0ea063d80b41/12933_2019_828_Fig1_HTML.jpg

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