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Abstract
Background and Objectives Diabetes mellitus (DM) contributes significantly to metabolic syndrome and cardiovascular events, and it may be a comorbidity of epilepsy. The objective of this study was to investigate whether long-term antiseizure medication (ASM) use is associated with the risk of developing type 2 diabetes.
Methods We analyzed data from the Chang Gung Research Database. Patients aged ≥45 years who received ASM treatment from January 2001 to May 2019 were identified. Patients with DM-associated diseases and short-term ASM use were excluded. The patients were classified into nonenzyme interaction, enzyme-inducing, enzyme-inhibiting, and mixed ASM groups. The rate of incident diabetes associated with individual ASM was further analyzed. Propensity score weighting was performed to balance between-group differences. Analyses were conducted with Cox proportional regression models and stabilized inverse probability of treatment weighting (IPTW). Hazard ratios (HRs) were calculated at 3, 4, 6, and 9 years after the index date and the end of follow-up.
Results A total of 5,103 patients were analyzed, of whom 474 took nonenzyme interaction ASMs, 1,156 took enzyme-inducing ASMs, 336 took enzyme-inhibiting ASMs, and 3,137 took mixed ASMs. During follow-up (39,248 person-years), 663 patients developed new-onset DM, and the prevalence was 13.0%. The incidence of DM plateaued at 6–9 years after ASM initiation. Enzyme-inhibiting ASMs were significantly associated with a higher HR starting at the third year and then throughout the study period. The HRs were 1.93 (95% CI 1.33–2.80), 1.85 (95% CI 1.24–2.75), and 2.08 (95% CI 1.43–3.03) in unadjusted, adjusted, and stabilized IPTW models, respectively, at the end of follow-up. The dosing of ASM did not increase the risk of DM, and none of the individual ASM analyses reached statistical significance.
Discussion The long-term use of enzyme-inhibiting ASMs was associated with an increased risk of incident DM, and the risk increased with the duration of treatment. These findings may guide the choice of drugs in those requiring long-term ASM therapy, particularly in high-risk individuals.
Classification of Evidence This study provides Class IV evidence that enzyme-inhibiting ASMs were associated with an increased risk of developing DM compared with nonenzyme interaction ASMs.
Glossary
- ASM=
- antiseizure medication;
- ASMD=
- absolute standardized mean difference;
- CGMH=
- Chang Gung Memorial Hospital;
- CGRD=
- Chang Gung Research Database;
- CYP=
- cytochrome P450;
- DDD=
- defined daily dose;
- DM=
- diabetes mellitus;
- GABA=
- γ-aminobutyric acid;
- HR=
- hazard ratio;
- ICD-9-CM=
- International Classification of Diseases, Ninth Revision, Clinical Modification;
- ICD-10-CM=
- International Classification of Diseases, Tenth Revision, Clinical Modification;
- IPTW=
- inverse probability of treatment weighting;
- WHO=
- World Health Organization
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editor was Associate Editor Barbara Jobst, MD, PhD, FAAN.
Class of Evidence: NPub.org/coe
- Received March 7, 2022.
- Accepted in final form February 9, 2023.
- © 2023 American Academy of Neurology
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