Antiepileptogenic Potential of Newer Glucose-lowering Drugs: A Meta-analysis
Abstract number :
3.001
Submission category :
1. Basic Mechanisms / 1A. Epileptogenesis of acquired epilepsies
Year :
2024
Submission ID :
198
Source :
www.aesnet.org
Presentation date :
12/9/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Udeept Sindhu, MBBS – Kasturba Medical College, Manipal, MAHE, India
Akshay Sharma, M.D. – Cleveland Clinic Epilepsy Center, Cleveland Clinic Foundation, Cleveland, OH, USA
Ifrah Zawar, MD, MS-CR – University of Virginia
Vineet Punia, MD – Cleveland Clinic
Rationale: Cardiovascular risk factors, including diabetes, significantly increase the risk of late-onset epilepsy, which represents a significant public health burden. Etiopathogenesis of late-onset epilepsy is thought to be a confluence of neurodegeneration and vascular damage. Emerging evidence suggests that newer Glucose-Lowering Drugs (GLDs), including Dipeptidyl Peptidase-4 (DPP-4) inhibitors, Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs), and Sodium-Glucose cotransporter-2 (SGLT2) inhibitors possess neuroprotective¹ and anti-inflammatory properties², which raises the intriguing possibility that these drugs may potentially impact seizures and epilepsy development. This meta-analysis aims to evaluate the potential anti-epileptogenic effects of these GLDs, hypothesizing that they reduce the risk of seizures and epilepsy.
Methods: A comprehensive search of PubMed was conducted to identify randomized placebo-controlled trials of newer GLDs for assessing cardiovascular and renal outcomes, which allowed for a longer duration of follow-up. Inclusion criteria encompassed trials involving adults (≥18 years) and reporting seizure or epilepsy events. Data from eligible trials were extracted, including participant characteristics, intervention details, follow-up duration, and adverse events. Pooled relative risks (RR) and odds ratios (OR) with 95% confidence intervals (CI) were calculated using the Mantel-Haenszel method. Subgroup and sensitivity analyses (using Peto’s method) were conducted to assess the robustness of findings.
Results: A total of 27 trials involving 197,907 participants were included (Table 1). Seizure events occurred in 118 (0.12%) placebo patients versus 108 (0.10%) GLD patients. Epilepsy events were reported in 56 (0.05%) placebo patients versus 45 (0.04%) GLD patients. The meta-analysis found a trend towards a reduced risk of seizures (OR=0.82, 95% CI: 0.63-1.06; p=0.13) and epilepsy (OR=0.75, 95% CI: 0.51-1.10; p=0.15) in patients receiving newer GLDs compared to placebo. Subgroup analysis revealed non-significant trends towards reduced seizures with GLP-1 RAs (OR=0.67, 95% CI: 0.42-1.07) and reduced epilepsy with DPP-4 inhibitors (OR=0.54, 95% CI: 0.25-1.19). No significant heterogeneity or publication bias was detected. Sensitivity analyses confirmed these trends.
Conclusions: Our meta-analysis suggests a potential anti-epileptogenic effect of newer GLDs, although findings were not statistically significant, which could be because seizure and epilepsy were not one of the predetermined outcome measures of interest in these trials. The neuroprotective mechanisms, such as reducing neuroinflammation and oxidative stress, support these trends. Given the supporting preclinical evidence and the trends observed in our meta-analysis, further research using large real-world datasets is warranted to validate these results.
References:
1. Pharmacol Res. 2022 Dec;186:106550.
2. Epilepsy Research, 142, 45–52.
Funding: None
Basic Mechanisms