Can Newer Glucose-Lowering Drugs Reduce Risk of Late-Onset Seizure and Epilepsy? A Meta-Analysis
Udeept Sindhu1, Akshay Sharma2, Ifrah Zawar3, Vineet Punia4
1Neurology, Kasturba Medical College, Manipal, India, 2Cleveland Clinic Foundations, 3University of Virginia School of Medicine, 4Cleveland Clinic
Background:
Current Anti-Seizure Medications cannot prevent or modify epilepsy progression, particularly in late-onset epilepsy (LOE), which often occurs after age 60 and is linked to cerebrovascular disease. New evidence suggests that newer glucose-lowering drugs (GLDs) may offer neuroprotective and anti-inflammatory benefits. Due to the shared mechanisms of neurodegeneration and vascular damage in LOE, we performed a meta-analysis to examine whether newer GLDs could offer protection against seizures and epilepsy.
Design/Methods:
We searched MEDLINE and Cochrane Central for trials comparing newer glucose-lowering drugs (Dipeptidyl Peptidase-4 inhibitors, Glucagon-Like Peptide-1 receptor agonists, Sodium-Glucose Cotransporter-2 inhibitors) to placebo, focusing on cardiovascular and renal outcomes with reported seizures or epilepsy. Data on adverse events were extracted, and study quality was assessed using the Cochrane risk of bias tool. Pooled relative risks and odds ratios were calculated using the Mantel-Haenszel method, with sensitivity analysis for low event rates and statistical significance set at p ≤ 0.05.
Results:
Twenty seven studies with almost 200,000 patients (mean age 64.9 years, 65.6% males) were included. Patients taking newer GLDs had a 24% lower risk of late-onset seizures and epilepsy, combined, (RR: 0.76, 95% CI: 0.62 to 0.95) and 22% lower risk of late-onset seizures only (RR = 0.78; 95% CI = 0.60-1.00), compared to patients on placebo. This seizure and epilepsy prevention benefit was only noted among patients taking GLP-1 receptor agonists (RR =0.67, 95% CI: 0.46-0.98).
Conclusions:
This meta-analysis suggests that newer glucose-lowering drugs, particularly the GLP-1 receptor agonist class, may protect against late-onset seizures and epilepsy. This is supported by evidence of their neuroprotective effects against cerebrovascular damage and neuroinflammation from emerging animal studies and human data. Future research is needed to confirm these findings, as late-onset epilepsy is a growing global issue that may benefit from preventative therapies.
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