目的:评估钠-葡萄糖协同转运蛋白-2(SGLT-2)抑制剂的比较有效性,胰高血糖素样肽-1(GLP-1)受体激动剂,和二肽基肽酶-4(DPP-4)抑制剂在常规临床实践中预防2型糖尿病患者的高钾血症。
方法:基于人群的积极比较队列研究,新的用户设计。
方法:2013年4月至2022年4月,来自美国医疗保险和两个大型商业保险数据库的索赔数据。
方法:1:1倾向评分与新服用SGLT-2抑制剂和DPP-4抑制剂的2型糖尿病成人相匹配(n=778908),GLP-1受体激动剂与DPP-4抑制剂(n=729820),和SGLT-2抑制剂与GLP-1受体激动剂(n=873460)。
方法:在住院或门诊患者中诊断为高钾血症。次要结果为高钾血症,定义为血清钾水平≥5.5mmol/L,在住院或急诊科诊断为高钾血症。
结果:与DPP-4抑制剂治疗相比,开始使用SGLT-2抑制剂治疗的高钾血症发生率较低(风险比0.75,95%置信区间(CI)0.73至0.78),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抑制剂低2.4%(95%CI2.1%至2.7%)(4.6%v7.0%),GLP-1受体激动剂比DPP-4抑制剂低1.8%(1.4%至2.1%)(5.7%v7.5%),SGLT-2抑制剂比GLP-1受体激动剂低1.2%(0.9%至1.5%)(4.7%v6.0%)。次要结局和按年龄定义的亚组之间的结果是一致的,性别,种族,医疗条件,其他药物使用,和血红蛋白A1c水平在相对尺度上。SGLT-2抑制剂和GLP-1受体激动剂在绝对规模上的益处对于心力衰竭患者来说是最大的。慢性肾病,或使用盐皮质激素受体拮抗剂的人。与DPP-4抑制剂相比,在SGLT-2抑制剂(canagliflozin,dapagliflozin,依帕列净)和GLP-1受体激动剂(杜拉鲁肽,艾塞那肽,利拉鲁肽,semaglutide)类。
结论:在2型糖尿病患者中,SGLT-2抑制剂和GLP-1受体激动剂在总体人群和相关亚组中与DPP-4抑制剂相比具有较低的高钾血症风险。SGLT-2抑制剂和GLP-1受体激动剂类别中各个药剂之间关联的一致性表明一类效应。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了它们在2型糖尿病患者中的应用。尤其是那些有高钾血症风险的人。
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.
Population based cohort
study with active-comparator, new user design.
Claims data from Medicare and two large commercial insurance databases in the United States from April 2013 to April 2022.
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).
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.
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.
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.