Department of Medicine, Division of Nephrology, University Health Network, Toronto, ON, Canada.
Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
Curr Diab Rep. 2022 Jul;22(7):317-332. doi: 10.1007/s11892-022-01471-2. Epub 2022 May 28.
The aim of this review is to summarize existing research investigating the use of sodium glucose cotransporter-2 (SGLT2) inhibitors in patients with type 1 diabetes mellitus (T1DM) while highlighting potential strategies to mitigate the risk of diabetic ketoacidosis (DKA).
SGLT2 inhibitors have been studied in patients with T1DM in phase 3 clinical trials such as the inTandem, DEPICT, and EASE trials, which demonstrated consistent reductions in HbA1c. Secondary analyses of these trials have also reported potential kidney protective effects that are independent of improved glycemic control. However, trials in patients with type 2 diabetes mellitus (T2DM) have found an increased risk of DKA with SGLT2 inhibitors, a serious concern in patients with T1DM. SGLT2 inhibitors provide cardiovascular benefits and kidney protection in patients with T2DM and are a promising therapeutic option for patients with T1DM due to overlapping pathophysiological mechanisms. However, SGLT2 inhibitors increase the risk of DKA, and there is currently a lack of research investigating the beneficial effects of SGLT2 inhibitors in patients with T1DM. Preventative measure for DKA would have to be implemented and the risks would need to be carefully balanced with the benefits offered by SGLT2 inhibitors. Additional research will also be required to determine the kidney protective effects of SGLT2 inhibitors in patients with T1DM and diabetic kidney disease and to quantify the risk of DKA after the implementation of preventative measures, proper patient education, and ketone monitoring.
本文旨在总结目前关于钠-葡萄糖协同转运蛋白 2（SGLT2）抑制剂在 1 型糖尿病（T1DM）患者中应用的研究，同时强调减轻糖尿病酮症酸中毒（DKA）风险的潜在策略。
SGLT2 抑制剂已在 T1DM 患者的 3 期临床试验中进行了研究，如 inTandem、DEPICT 和 EASE 试验，这些试验均显示 HbA1c 持续降低。这些试验的二次分析也报告了潜在的肾脏保护作用，与改善血糖控制无关。然而，在 2 型糖尿病（T2DM）患者中进行的试验发现 SGLT2 抑制剂会增加 DKA 的风险，这在 T1DM 患者中是一个严重的问题。SGLT2 抑制剂在 T2DM 患者中提供心血管益处和肾脏保护作用，并且由于重叠的病理生理机制，是 T1DM 患者有前途的治疗选择。然而，SGLT2 抑制剂会增加 DKA 的风险，目前缺乏研究调查 SGLT2 抑制剂在 T1DM 患者中的有益作用。必须采取预防 DKA 的措施，并且需要仔细平衡 SGLT2 抑制剂带来的风险与益处。还需要进行更多的研究，以确定 SGLT2 抑制剂在 T1DM 和糖尿病肾病患者中的肾脏保护作用，并在实施预防措施、适当的患者教育和酮体监测后量化 DKA 的风险。
