Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.
Leviev Heart Center, Sheba Medical Center, Derech Sheba 2, Ramat Gan, Israel.
Eur J Prev Cardiol. 2022 Jul 20;29(9):1334-1342. doi: 10.1093/eurjpc/zwab209.
While genetic and biological studies indicated a potential association between proprotein-convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and hyperglycaemia, real-world data are limited. Therefore, we sought to investigate this association using the FDA adverse event reporting system (FAERS).
The FAERS database (2015-2020) was retrospectively queried to characterize reporting of hyperglycaemic adverse events (AEs) with PCSK9i. Disproportionality analyses were performed using the adjusted reporting odds ratio (adj.ROR), and the lower bound of the information component (IC) 95% credibility interval (IC025 > 0 is deemed significant). Among 7 295 624 eligible patients, 71 748 reports of evolocumab and 15 976 of alirocumab were identified. Compared to the full database, PCSK9i treatment was associated with increased reporting of hyperglycaemic AEs [n = 1841, adj.ROR = 1.14 (1.07-1.22), IC025 = 0.13]. Hyperglycaemic AEs were primarily mild hyperglycaemia [n = 1469, adj. ROR = 1.48 (1.36-1.62), IC025 = 0.51] rather than diabetes [n = 372, adj. ROR = 0.67 (0.60-0.74), IC025 = -0.90]. Among PCSK9i agents, evolocumab, but not alirocumab, was associated with hyperglycaemic AEs [n = 1587, adj. ROR = 1.24 (1.15-1.32), IC025 = 0.20; n = 254, adj. ROR = 0.73 (0.60-0.88), IC025 = -0.38, respectively]. Hyperglycaemic AEs were reported more often with PCSK9i compared to ezetimibe [adj.ROR = 1.99 (1.35-2.94)], and less often compared to statins [adj.ROR = 0.26 (0.25-0.28)]. Notably, hyperglycaemic AEs were reported more frequently by diabetic than by non-diabetic patients (P < 0.001), mostly occurred within 6 months of treatment and were reversible upon drug discontinuation.
In a real-world setting, PCSK9i treatment was associated with increased reporting of mild hyperglycaemia, but not diabetes. While initial monitoring is warranted, the favourable glycaemic safety profile compared to statins supports their essential role in the management of lipid disorders.
虽然遗传和生物学研究表明，前蛋白转化酶枯草溶菌素/柯萨奇蛋白酶 9 抑制剂（PCSK9i）与高血糖之间可能存在关联，但实际数据有限。因此，我们试图利用食品和药物管理局不良事件报告系统（FAERS）来研究这种关联。
对 FAERS 数据库（2015-2020 年）进行回顾性查询，以描述 PCSK9i 相关的高血糖不良事件（AE）报告情况。采用调整后的报告比值比（adj.ROR）进行比例失衡分析，信息成分（IC）95%置信区间的下限（IC025＞0 被认为具有统计学意义）。在 7295624 名合格患者中，鉴定出 71748 例依洛尤单抗和 15976 例阿利西尤单抗的报告。与整个数据库相比，PCSK9i 治疗与高血糖 AE 的报告增加相关[n=1841，adj.ROR=1.14（1.07-1.22），IC025=0.13]。高血糖 AE 主要为轻度高血糖[n=1469，adj.ROR=1.48（1.36-1.62），IC025=0.51]，而非糖尿病[n=372，adj.ROR=0.67（0.60-0.74），IC025=-0.90]。在 PCSK9i 药物中，与高血糖 AE 相关的是依洛尤单抗，而非阿利西尤单抗[n=1587，adj.ROR=1.24（1.15-1.32），IC025=0.20；n=254，adj.ROR=0.73（0.60-0.88），IC025=-0.38]。与依折麦布相比，PCSK9i 治疗报告的高血糖 AE 更常见[adj.ROR=1.99（1.35-2.94）]，与他汀类药物相比则更少[adj.ROR=0.26（0.25-0.28）]。值得注意的是，与非糖尿病患者相比，糖尿病患者报告高血糖 AE 的频率更高（P＜0.001），大多发生在治疗后 6 个月内，且停药后可逆转。
在真实世界环境中，PCSK9i 治疗与轻度高血糖的报告增加相关，但与糖尿病无关。虽然需要初始监测，但与他汀类药物相比，其血糖安全性更优，这支持了它们在脂质紊乱管理中的重要作用。
