Kao David P, Martin James L, Aquilante Christina L, Shalowitz Elise L, Leyba Katarina, Kudron Elizabeth, Reusch Jane E B, Regensteiner Judith G
Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
Ludeman Family Center for Women's Health Research, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
BMJ Open Diabetes Res Care. 2024 Dec 5;12(6):e004343. doi: 10.1136/bmjdrc-2024-004343.
Diabetes mellitus (DM) is increasingly recognized as a possible consequence of statin therapy. Secondary analysis of randomized clinical trials and limited observational cohort analyses have suggested that women may be more likely than men to experience statin-associated DM. No analyses of real-world drug safety data addressing this question have been published.
This was a retrospective pharmacovigilance analysis of spontaneously reported adverse drug events (ADEs) submitted to the Food and Drug Administration Adverse Event Reporting System between January 1997 through December 2023. We analyzed cases that mentioned atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin in aggregate as well as cases reporting atorvastatin, pravastatin, rosuvastatin, simvastatin individually. DM events were identified using the Medical Dictionary for Regulatory Activities. We used the proportional reporting ratio to identify increased rates of statin-associated DM events in women and men compared with all other medications, and the reporting OR to compare reporting rates in women versus men.
A total of 18,294,814 ADEs were reported during the study period. Among statin-associated ADEs, 14,874/519,209 (2.9%) reports mentioned DM in women compared with 7,411/489,453 (1.5%) in men, which were both significantly higher than background (0.6%). Statins were the primary-suspected or secondary-suspected cause of the ADE significantly more often in women than men (60 vs 30%), and reporting rates were disproportionately higher in women than in men for all statins. (reporting OR 1.9 (95% CI 1.9 to 2.0)). The largest difference in reporting of statin-associated DM between women and women was observed with atorvastatin.
Analysis of post-marketing spontaneous ADE reports demonstrated a higher reporting rate of DM-associated with statin use compared with other medications with a significantly higher reporting rate in women compared with men. Future studies should consider mechanisms of statin-associated DM moderated by sex.
糖尿病（DM）日益被认为是他汀类药物治疗可能产生的后果。随机临床试验的二次分析和有限的观察性队列分析表明，女性可能比男性更易出现与他汀类药物相关的糖尿病。尚未发表针对这一问题的真实世界药物安全性数据的分析。
这是一项回顾性药物警戒分析，分析了1997年1月至2023年12月期间提交给美国食品药品监督管理局不良事件报告系统的自发报告的药物不良事件（ADE）。我们分析了总体提及阿托伐他汀、氟伐他汀、洛伐他汀、匹伐他汀、普伐他汀、瑞舒伐他汀或辛伐他汀的病例，以及单独报告阿托伐他汀、普伐他汀、瑞舒伐他汀、辛伐他汀的病例。使用《医学监管活动词典》识别糖尿病事件。我们使用比例报告比来确定与所有其他药物相比，女性和男性中与他汀类药物相关的糖尿病事件的发生率增加情况，并使用报告比值比来比较女性与男性的报告率。
在研究期间共报告了18,294,814例药物不良事件。在与他汀类药物相关的药物不良事件中，女性有14,874/519,209（2.9%）的报告提及糖尿病，男性为7,411/489,453（1.5%），两者均显著高于背景值（0.6%）。他汀类药物作为药物不良事件的主要怀疑或次要怀疑原因在女性中显著多于男性（60%对30%），并且所有他汀类药物在女性中的报告率均不成比例地高于男性（报告比值比1.9（95%置信区间1.9至2.0））。在阿托伐他汀方面，观察到女性与他汀类药物相关糖尿病报告的差异最大。
对上市后自发药物不良事件报告的分析表明，与其他药物相比，与他汀类药物使用相关的糖尿病报告率更高，女性的报告率显著高于男性。未来的研究应考虑性别对他汀类药物相关糖尿病的影响机制。
