Objectives To evaluate the comparative effectiveness of sodium-glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors in preventing hyperkalemia in people with type 2 diabetes in routine clinical practice. Design Population based cohort study with active-comparator, new user design. Setting Claims data from Medicare and two large commercial insurance databases in the United States from April 2013 to April 2022. Participants 1:1 propensity score matched adults with type 2 diabetes newly starting SGLT-2 inhibitors versus DPP-4 inhibitors (n=778 908), GLP-1 receptor agonists versus DPP-4 inhibitors (n=729 820), and SGLT-2 inhibitors versus GLP-1 receptor agonists (n=873 460). Main outcome measures Hyperkalemia diagnosis in the inpatient or outpatient setting. Secondary outcomes were hyperkalemia defined as serum potassium levels ≥5.5 mmol/L and hyperkalemia diagnosis in the inpatient or emergency department setting. Results Starting SGLT-2 inhibitor treatment was associated with a lower rate of hyperkalemia than DPP-4 inhibitor treatment (hazard ratio 0.75, 95% confidence interval (CI) 0.73 to 0.78) and a slight reduction in rate compared with GLP-1 receptor agonists (0.92, 0.89 to 0.95). Use of GLP-1 receptor agonists was associated with a lower rate of hyperkalemia than DPP-4 inhibitors (0.79, 0.77 to 0.82). The three year absolute risk was 2.4% (95% CI 2.1% to 2.7%) lower for SGLT-2 inhibitors than DPP-4 inhibitors (4.6% v 7.0%), 1.8% (1.4% to 2.1%) lower for GLP-1 receptor agonists than DPP-4 inhibitors (5.7% v 7.5%), and 1.2% (0.9% to 1.5%) lower for SGLT-2 inhibitors than GLP-1 receptor agonists (4.7% v 6.0%). Findings were consistent for the secondary outcomes and among subgroups defined by age, sex, race, medical conditions, other drug use, and hemoglobin A1c levels on the relative scale. Benefits for SGLT-2 inhibitors and GLP-1 receptor agonists on the absolute scale were largest for those with heart failure, chronic kidney disease, or those using mineralocorticoid receptor antagonists. Compared with DPP-4 inhibitors, the lower rate of hyperkalemia was consistently observed across individual agents in the SGLT-2 inhibitor (canagliflozin, dapagliflozin, empagliflozin) and GLP-1 receptor agonist (dulaglutide, exenatide, liraglutide, semaglutide) classes. Conclusions In people with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists were associated with a lower risk of hyperkalemia than DPP-4 inhibitors in the overall population and across relevant subgroups. The consistency of associations among individual agents in the SGLT-2 inhibitor and GLP-1 receptor agonist classes suggests a class effect. These ancillary benefits of SGLT-2 inhibitors and GLP-1 receptor agonists further support their use in people with type 2 diabetes, especially in those at risk of hyperkalemia. A data use agreement is required for each of these data sources. These data use agreements do not permit the authors to share patient level source data or data derivatives with individuals and institutions not covered under the data use agreements. The databases used in this study are accessible to other researchers by contacting the data providers and acquiring data use agreements or licenses.

中文翻译：

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SGLT-2 抑制剂、GLP-1 受体激动剂和 DPP-4 抑制剂与临床实践中 2 型糖尿病患者高钾血症的风险：基于人群的队列研究


目的 评估钠-葡萄糖协同转运蛋白 2 (SGLT-2) 抑制剂、胰高血糖素样肽 1 (GLP-1) 受体激动剂和二肽基肽酶 4 (DPP-4) 抑制剂预防人类高钾血症的比较效果常规临床实践中患有 2 型糖尿病的患者。使用主动比较器、新用户设计设计基于人群的队列研究。设置 2013 年 4 月至 2022 年 4 月期间美国 Medicare 和两个大型商业保险数据库的索赔数据。参与者 1:1 倾向评分将新开始使用 SGLT-2 抑制剂与 DPP-4 抑制剂的 2 型糖尿病成人进行匹配（n=778 908） ），GLP-1 受体激动剂与 DPP-4 抑制剂（n=729 820），以及 SGLT-2 抑制剂与 GLP-1 受体激动剂（n=873 460）。主要结局指标是住院或门诊的高钾血症诊断。次要结局是高钾血症，定义为血清钾水平≥5.5 mmol/L，以及在住院或急诊室诊断为高钾血症。结果 与 DPP-4 抑制剂治疗相比，开始 SGLT-2 抑制剂治疗与较低的高钾血症发生率相关（风险比 0.75，95% 置信区间 (CI) 0.73 至 0.78），并且与 GLP-1 受体激动剂相比，发生率略有降低（0.92、0.89 至 0.95）。与 DPP-4 抑制剂相比，使用 GLP-1 受体激动剂与较低的高钾血症发生率相关（0.79、0.77 至 0.82）。 SGLT-2 抑制剂的三年绝对风险比 DPP-4 抑制剂（4.6% vs 7.0%）低 2.4%（95% CI 2.1% 至 2.7%），GLP 低 1.8%（1.4% 至 2.1%） 1 受体激动剂比 DPP-4 抑制剂低（5.7% 对 7.5%），SGLT-2 抑制剂比 GLP-1 受体激动剂低 1.2%（0.9% 至 1.5%）（4.7% 对 6.0%）。 次要结局以及按年龄、性别、种族、医疗状况、其他药物使用和相对规模的糖化血红蛋白水平定义的亚组之间的结果是一致的。对于患有心力衰竭、慢性肾病或使用盐皮质激素受体拮抗剂的患者来说，SGLT-2 抑制剂和 GLP-1 受体激动剂的绝对获益最大。与 DPP-4 抑制剂相比，SGLT-2 抑制剂（卡格列净、达格列净、恩格列净）和 GLP-1 受体激动剂（度拉鲁肽、艾塞那肽、利拉鲁肽、索马鲁肽）类药物的高钾血症发生率始终较低。结论 在 2 型糖尿病患者中，在总体人群和相关亚组中，SGLT-2 抑制剂和 GLP-1 受体激动剂与高钾血症风险低于 DPP-4 抑制剂相关。 SGLT-2 抑制剂和 GLP-1 受体激动剂类别中各个药物之间关联的一致性表明存在类别效应。 SGLT-2 抑制剂和 GLP-1 受体激动剂的这些辅助益处进一步支持它们在 2 型糖尿病患者中的使用，尤其是有高钾血症风险的患者。每个数据源都需要数据使用协议。这些数据使用协议不允许作者与数据使用协议未涵盖的个人和机构共享患者级别的源数据或数据衍生品。其他研究人员可以通过联系数据提供商并获取数据使用协议或许可证来访问本研究中使用的数据库。