Movement disorders related to antidiabetic medications: a real-world pharmacovigilance study

IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY
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Abstract

Background

Diabetic Mellitus (DM) has progressively emerged as a worldwide health problem, leading to the widespread deployment of antidiabetic drugs as the primary therapy in the global population. The incidence of diabetes medications-related movement disorders (drMD) is noteworthy but underestimated by clinical practitioners.

Research design and Methods

In order to address the incidence of drMD in DM patients and realize the serious outcomes associated with drMD, we conducted a real-world pharmacovigilance study of 612,043 DM patients using the FDA Adverse Event Reporting System (FAERS) database from January 2004 to September 2023. Reporting Odd Ratio (ROR) was calculated to reflect the risk of drMD. A multivariable logistic regression analysis was employed to adjust crude ROR with the mixed factors including age, sex and various antidiabetic treatments. Afterward, a Mendelian Randomization (MR) study was performed to elucidate the underlying genetic correlation between the genetically proxied targets of antidiabetic drugs and motor disorders.

Results

Among 11,729 cases of motor adverse events in DM patients, six categories of drMD were significantly associated with DM medications. Noticeably, metformin was revealed to drastically increase the incidence of parkinsonism (adjusted ROR:3.97; 95 %CI (3.03, 5.19), p = 5.68e-24), bradykinesia (adjusted ROR:1.69; 95 %CI (1.07,2.59), p = 0.02) and irregular hyperkinesia, including chorea, choreoathetosis and athetosis. Insulin/insulin analogues and GLP-1 analogues presented notably higher odds of tremor: the adjusted ROR (aROR) of insulin and GLP-1 analogue is respectively 1.24 (95 %CI (1.15,1.34), p = 2.51e-08) and 1.78 (95 %CI (1.65,1.91), p = 5.64e-54). The combined therapeutic effects of multiple genetic variants of metformin, especially AMP-activated protein kinase (AMPK) were markedly linked to a greater likelihood of developing secondary parkinsonism (OR:10.816, p = 0.049) according to MR analyses.

Conclusion

The use of antidiabetic medications was significantly related to an increased incidence of movement disorders in DM patients. Moreover, MR analyses provided further genetic evidence for the pharmacovigilance study. This comprehensive investigation might help physicians recognize neurological adverse events associated with antidiabetic treatments and administer effective interventions.

与抗糖尿病药物有关的运动障碍:一项真实世界药物警戒研究
背景糖尿病(Diabetic Mellitus,DM)已逐渐成为一个世界性的健康问题,导致全球人口广泛使用抗糖尿病药物作为主要治疗手段。为了了解糖尿病药物相关运动障碍(drMD)在糖尿病患者中的发生率,并认识到与 drMD 相关的严重后果,我们利用美国食品药物管理局不良事件报告系统(FAERS)数据库,对 2004 年 1 月至 2023 年 9 月期间的 612,043 名糖尿病患者进行了真实世界药物警戒研究。计算了报告奇异比 (ROR),以反映发生 drMD 的风险。采用多变量逻辑回归分析,用年龄、性别和各种抗糖尿病治疗等混合因素调整粗略 ROR。结果在11729例DM患者的运动不良事件中,有6类drMD与DM药物显著相关。值得注意的是,二甲双胍可显著增加帕金森病(调整后ROR:3.97;95 %CI (3.03,5.19),p = 5.68e-24)、运动迟缓(调整后ROR:1.69;95 %CI (1.07,2.59),p = 0.02)和不规则运动过多症(包括舞蹈症、舞蹈症和失动症)的发病率。胰岛素/胰岛素类似物和 GLP-1 类似物出现震颤的几率明显更高:胰岛素和 GLP-1 类似物的调整 ROR(aROR)分别为 1.24(95 %CI (1.15,1.34),p = 2.51e-08)和 1.78(95 %CI (1.65,1.91),p = 5.64e-54)。根据 MR 分析,二甲双胍多种基因变异的综合治疗效果,尤其是 AMP 激活蛋白激酶 (AMPK) 的综合治疗效果,与继发性帕金森病发病率的增加密切相关(OR:10.816, p = 0.049)。此外,磁共振分析为药物警戒研究提供了进一步的遗传学证据。这项全面的调查可能有助于医生识别与抗糖尿病治疗相关的神经系统不良事件,并采取有效的干预措施。
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来源期刊
CiteScore
12.00
自引率
1.80%
发文量
153
审稿时长
56 days
期刊介绍: Progress in Neuro-Psychopharmacology & Biological Psychiatry is an international and multidisciplinary journal which aims to ensure the rapid publication of authoritative reviews and research papers dealing with experimental and clinical aspects of neuro-psychopharmacology and biological psychiatry. Issues of the journal are regularly devoted wholly in or in part to a topical subject. Progress in Neuro-Psychopharmacology & Biological Psychiatry does not publish work on the actions of biological extracts unless the pharmacological active molecular substrate and/or specific receptor binding properties of the extract compounds are elucidated.
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