Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
JAMA Intern Med. 2024 Oct 1;184(10):1195-1203. doi: 10.1001/jamainternmed.2024.3806.
IMPORTANCE: Hyperkalemia is a common complication in people with type 2 diabetes (T2D) that may limit the use of guideline-recommended renin-angiotensin system inhibitors (RASis). Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs) increase urinary potassium excretion, which may translate into reduced hyperkalemia risk. OBJECTIVE: To compare rates of hyperkalemia and RASi persistence among new users of GLP-1RAs vs dipeptidyl peptidase-4 inhibitors (DPP-4is). DESIGN, SETTING, AND PARTICIPANTS: This cohort study included all adults with T2D in the region of Stockholm, Sweden, who initiated GLP-1RA or DPP-4i treatment between January 1, 2008, and December 31, 2021. Analyses were conducted between October 1, 2023, and April 29, 2024. EXPOSURES: GLP-1RAs or DPP-4is. MAIN OUTCOMES AND MEASURES: The primary study outcome was time to any hyperkalemia (potassium level >5.0 mEq/L) and moderate to severe (potassium level >5.5 mEq/L) hyperkalemia. Time to discontinuation of RASi use among individuals using RASis at baseline was assessed. Inverse probability of treatment weights served to balance more than 70 identified confounders. Marginal structure models were used to estimate per-protocol hazard ratios (HRs). RESULTS: A total of 33 280 individuals (13 633 using GLP-1RAs and 19 647 using DPP-4is; mean [SD] age, 63.7 [12.6] years; 19 853 [59.7%] male) were included. The median (IQR) time receiving treatment was 3.9 (1.0-10.9) months. Compared with DPP-4i use, GLP-1RA use was associated with a lower rate of any hyperkalemia (HR, 0.61; 95% CI, 0.50-0.76) and moderate to severe (HR, 0.52; 95% CI, 0.28-0.84) hyperkalemia. Of 21 751 participants who were using RASis, 1381 discontinued this therapy. The use of GLP-1RAs vs DPP-4is was associated with a lower rate of RASi discontinuation (HR, 0.89; 95% CI, 0.82-0.97). Results were consistent in intention-to-treat analyses and across strata of age, sex, cardiovascular comorbidity, and baseline kidney function. CONCLUSIONS: In this study of patients with T2D managed in routine clinical care, the use of GLP-1RAs was associated with lower rates of hyperkalemia and sustained RASi use compared with DPP-4i use. These findings suggest that GLP-1RA treatment may enable wider use of guideline-recommended medications and contribute to clinical outcomes in this population.
重要性：高钾血症是 2 型糖尿病（T2D）患者的常见并发症，可能限制指南推荐的肾素-血管紧张素系统抑制剂（RASi）的使用。新出现的证据表明，胰高血糖素样肽-1 受体激动剂（GLP-1RAs）增加尿钾排泄，这可能转化为降低高钾血症风险。 目的：比较 GLP-1RA 与二肽基肽酶-4 抑制剂（DPP-4is）新使用者的高钾血症和 RASi 持续使用率。 设计、设置和参与者：这项队列研究纳入了瑞典斯德哥尔摩地区所有 T2D 成年人，他们在 2008 年 1 月 1 日至 2021 年 12 月 31 日期间开始 GLP-1RA 或 DPP-4i 治疗。分析于 2023 年 10 月 1 日至 2024 年 4 月 29 日进行。 暴露：GLP-1RAs 或 DPP-4is。 主要结局和测量：主要研究结局为任何高钾血症（血钾水平>5.0 mEq/L）和中重度高钾血症（血钾水平>5.5 mEq/L）的发生时间。评估了基线时使用 RASi 的个体中 RASi 停用的时间。逆概率治疗权重用于平衡 70 多个确定的混杂因素。边际结构模型用于估计按方案的危险比（HR）。 结果：共纳入 33280 名患者（13633 名使用 GLP-1RAs，19647 名使用 DPP-4is；平均[SD]年龄为 63.7[12.6]岁；19647 名[59.7%]男性）。接受治疗的中位（IQR）时间为 3.9（1.0-10.9）个月。与 DPP-4i 相比，GLP-1RA 治疗与较低的任何高钾血症发生率（HR，0.61；95%CI，0.50-0.76）和中重度高钾血症发生率（HR，0.52；95%CI，0.28-0.84）相关。在 21751 名使用 RASi 的参与者中，有 1381 人停止了该治疗。与 DPP-4i 相比，GLP-1RA 的使用与 RASi 停药率较低相关（HR，0.89；95%CI，0.82-0.97）。意向治疗分析和年龄、性别、心血管合并症和基线肾功能的各层结果一致。 结论：在这项常规临床护理中 2 型糖尿病患者的研究中，与 DPP-4i 相比，GLP-1RA 治疗与较低的高钾血症发生率和持续的 RASi 使用率相关。这些发现表明，GLP-1RA 治疗可能使指南推荐的药物更广泛使用，并有助于该人群的临床结局。
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