Sodium-glucose co-transporter-2 (SGLT2) inhibitors have several beneficial effects in patients with type 2 diabetes, including glucose lowering, weight loss, blood pressure lowering, and a reduced risk of major adverse cardiovascular events. To address high unmet medical need via improved glycaemic control, several clinical trials have been done to assess the efficacy and safety of SGLT2 inhibitors in combination with insulin therapy in patients with type 1 diabetes. In this Personal View, we summarise data from eight clinical trials of canagliflozin, dapagliflozin, empagliflozin, and sotagliflozin in patients with type 1 diabetes. HbA1c-lowering efficacy was greatest at 8-12 weeks of therapy, but the magnitude of HbA1c lowering waned with longer duration of treatment (up to 52 weeks). Data are not yet available to establish for how long glycaemic efficacy could be sustained during long-term therapy in patients with type 1 diabetes. Moreover, SGLT2 inhibitor therapy induces serious adverse events, including a roughly six-times increased risk of diabetic ketoacidosis. The US Food and Drug Administration estimated that one additional case of ketoacidosis will occur for every 26 patient-years of exposure of patients with type 1 diabetes to sotagliflozin therapy. Assuming a case mortality of 0·4%, this estimate translates into 16 additional deaths per year per 100 000 patients with type 1 diabetes undergoing treatment. These considerations raise important questions about the risk-to-benefit profile of SGLT2 inhibitors when used as adjunctive therapy in patients with type 1 diabetes.

中文翻译：

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SGLT2抑制剂作为1型糖尿病的辅助治疗：平衡收益和风险。

钠葡萄糖共转运蛋白2（SGLT2）抑制剂对2型糖尿病患者具有多种有益作用，包括降低血糖，减轻体重，降低血压以及降低重大不良心血管事件的风险。为了通过改善的血糖控制解决未满足的医疗需求，已经进行了多项临床试验来评估SGLT2抑制剂与胰岛素治疗相结合对1型糖尿病患者的疗效和安全性。在此个人观点中，我们总结了canagliflozin，dapagliflozin，empagliflozin和sotagliflozin在1型糖尿病患者中进行的八项临床试验的数据。降低HbA1c的功效在治疗的8-12周时最大，但随着治疗时间的延长（最长52周），降低HbA1c的幅度逐渐减弱。尚无数据可确定1型糖尿病患者在长期治疗期间可维持多长时间的血糖功效。此外，SGLT2抑制剂疗法可引起严重的不良事件，包括糖尿病性酮症酸中毒的风险增加约六倍。美国食品和药物管理局估计，在1型糖尿病患者接受sotagliflozin治疗的每26个患者年中，还会发生另一例酮症酸中毒。假设病死率为0·4％，则该估计数意味着每10万正在接受治疗的1型糖尿病患者每年增加16例死亡。这些考虑因素引发了有关将SGLT2抑制剂用作1型糖尿病患者辅助治疗的风险-获益特征的重要问题。