AIMS To investigate the risk of hyperkalemia in new users of sodium-glucose cotransporter 2 (SGLT2) inhibitors versus dipeptidyl peptidase-4 (DPP-4) inhibitors among patients with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS Patients with T2DM who commenced treatment with an SGLT2 or DPP-4 inhibitor between 2015 and 2019 were collected. A multivariable Cox proportional hazards analysis was applied to compare the risk of central laboratory-determined severe hyperkalemia, hyperkalemia, hypokalemia (serum potassium ≥ 6.0 mmol/L, ≥5.5 mmol/L, and < 3.5 mmol/L, respectively), and initiation of a potassium binder in patients newly prescribed an SGLT2 or DPP-4 inhibitor. 28 599 patients (mean age 60 ± 11 years, 60.9% male) were included after 1:2 propensity score matching, of whom 10 586 were new users of SGLT2 inhibitors and 18 013 DPP-4 inhibitors. During a 2-year follow-up, severe hyperkalemia developed in 122 SGLT2 inhibitor users and 325 DPP-4 inhibitor users. Use of SGLT2 inhibitors was associated with a 29% reduction in incident severe hyperkalemia (HR 0.71, 95%CI 0.58-0.88) compared with DPP-4 inhibitors. Risk of hyperkalemia (HR 0.81, 95%CI 0.71-0.92) and prescription of a potassium binder (HR 0.74, 95%CI 0.67-0.82) were likewise decreased with SGLT2 inhibitors compared with DPP-4 inhibitors. Occurrence of incident hypokalemia was nonetheless similar between those prescribed an SGLT2 inhibitor or a DPP-4 inhibitor (HR 0.90, 95%CI 0.81-1.01). CONCLUSION Our study provides real-world evidence that compared with DPP-4 inhibitors, SGLT2 inhibitors were associated with lower risk of hyperkalemia, and did not increase the incidence of hypokalemia in patients with T2DM.

中文翻译：

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服用 SGLT2 与 DPP-4 抑制剂的 2 型糖尿病患者发生高钾血症的风险。

目的 调查 2 型糖尿病 (T2DM) 患者中新使用者钠-葡萄糖协同转运蛋白 2 (SGLT2) 抑制剂与二肽基肽酶 4 (DPP-4) 抑制剂的高钾血症风险。方法和结果 收集 2015 年至 2019 年间开始接受 SGLT2 或 DPP-4 抑制剂治疗的 T2DM 患者。采用多变量 Cox 比例风险分析来比较中心实验室确定的严重高钾血症、高钾血症、低钾血症（血清钾分别≥ 6.0 mmol/L、≥5.5 mmol/L 和 < 3.5 mmol/L）和开始治疗的风险在新开出 SGLT2 或 DPP-4 抑制剂处方的患者中使用钾结合剂。经过1:2倾向评分匹配后，纳入了28 599名患者（平均年龄60±11岁，60.9%男性），其中10 586名是SGLT2抑制剂的新使用者，18 013名是DPP-4抑制剂的新使用者。在为期 2 年的随访中，122 名 SGLT2 抑制剂使用者和 325 名 DPP-4 抑制剂使用者出现严重高钾血症。与 DPP-4 抑制剂相比，使用 SGLT2 抑制剂可使严重高钾血症发生率降低 29%（HR 0.71，95%CI 0.58-0.88）。与 DPP-4 抑制剂相比，SGLT2 抑制剂同样降低了高钾血症风险（HR 0.81，95%CI 0.71-0.92）和钾结合剂处方（HR 0.74，95%CI 0.67-0.82）。尽管如此，服用 SGLT2 抑制剂或 DPP-4 抑制剂的患者发生低钾血症的情况相似（HR 0.90，95%CI 0.81-1.01）。结论 我们的研究提供了真实世界的证据，表明与 DPP-4 抑制剂相比，SGLT2 抑制剂与较低的高钾血症风险相关，并且不会增加 T2DM 患者低钾血症的发生率。