{"title":"Movement disorders related to antidiabetic medications: a real-world pharmacovigilance study","authors":"","doi":"10.1016/j.pnpbp.2024.111128","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>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.</p></div><div><h3>Research design and Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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), <em>p</em> = 5.68e-24), bradykinesia (adjusted ROR:1.69; 95 %CI (1.07,2.59), <em>p</em> = 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), <em>p</em> = 2.51e-08) and 1.78 (95 %CI (1.65,1.91), <em>p</em> = 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, <em>p</em> = 0.049) according to MR analyses.</p></div><div><h3>Conclusion</h3><p>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.</p></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0278584624001969","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
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.
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.