Pauline Anderson
December 17, 2024
LOS ANGELES — Newer glucose-lowering drugs reduce the risk for late-onset seizures and epilepsy by 24%, with glucagon-like peptide 1 receptor agonists (GLP-1 RAs) cutting the risk by 33%, according to a new meta-analysis.
These results are “amazing” considering there are currently no drugs that actually prevent epilepsy, lead study author Udeept Sindhu, MD, junior resident, Kasturba Medical College, Manipal, India, told Medscape Medical News.
Udeept Sindhu, MD
This kind of research could contribute to “bringing down the epilepsy burden worldwide,” said Sindhu.
The findings were presented on December 9, 2024, at the American Epilepsy Society (AES) 78th Annual Meeting 2024 and published online last month in Epilepsia Open.
The investigators looked at late-onset seizures and epilepsy (defined as diagnosed after age 55 years) in three classes of glucose-lowering drugs: GLP-1 RAs, dipeptidyl peptidase 4 (DPP-4) inhibitors, and sodium-glucose transport protein 2 (SGLT2) inhibitors.
While not “brand new,” these glucose-lowering drugs were introduced between 2000 and 2010 and represent “modern advances” compared with older medicines such metformin and sulfonylureas, said Sindhu. He added these “newer” agents are more apt to decrease neuroinflammation.
The meta-analysis included 27 randomized controlled trials of these drugs with a total population of 197,910 adults (102,939 randomized to receive the drug and 94,971 randomized to receive placebo). The analysis included five trials for DPP-4 inhibitors, eight for GLP-1 RAs, and 14 for SGLT2 inhibitors. The oldest trial was in 2013 and the most recent in 2023.
The studies investigated cardiovascular and renal outcomes and reported seizure or epilepsy as adverse events.
The three classes of drugs together reduced the risk for epilepsy and seizures (combined) by 24% (risk ratio [RR], 0.76; 95% CI, 0.62-0.95).
Looking at the classes individually, the RRs were 0.67 (95% CI, 0.46-0.98) for GLP-1 RAs, 0.74 (95% CI, 0.46-1.20) for DPP-4 inhibitors, and 0.85 (95% CI, 0.62-1.17) for SGLT2 inhibitors.
When investigating outcomes for epilepsy and seizures separately, there was a significant seizure risk reduction with GLP-1 RAs, but the results did not reach significance for epilepsy. This might be due to relatively short study durations or definitions of epilepsy used, said Sindhu.
The average follow-up in the studies was about 2.5 years, during which time more patients were diagnosed with a seizure than with epilepsy. And it’s unclear if the reviewed studies used the International League Against Epilepsy’s definition of epilepsy (two unprovoked seizures or one unprovoked seizure with a prior brain injury), said Sindhu.
As the combined outcomes of seizures and epilepsy were significant, and due to supportive preclinical data, “we propose these drugs might have anti-epileptogenic effects,” he said.
The most likely mechanism for these effects is through the overall cerebrovascular impact of these drugs, said Sindhu. “The most common cause of seizure and epilepsy in older adults is cerebrovascular disease, followed by neurodegenerative pathology.”
He noted these medications have been shown to reduce the risk for all-cause dementia, significantly slowing down neurodegeneration and improving neuroinflammation.
It’s too early to suggest clinicians reach for GLP-1 RA prescriptions for all older patients to prevent epilepsy. However, given this encouraging evidence, they could consider this drug class in patients with cerebrovascular risk factors, said Sindhu.
Generic versions are available, or emerging, for DPP-4 inhibitors and some SGLT2 inhibitors, he added. “To the best of my knowledge, only one GLP-1 agonist generic is available.”
Interesting and Promising
Commenting on the research, Daniel M. Goldenholz, MD, PhD, assistant professor of neurology, Beth Israel Deaconess Medical Center, Boston, said the meta-analysis approach used “is pretty interesting,” and the results “seem promising.”
The researchers address the question of whether lowering glucose levels in these older patients decreases the risk, or delays development, of epilepsy, and their results suggest the answer to that question “is perhaps yes,” said Goldenholz.
“This is a very important question now that we’re finding more and more that cardiovascular risk factors appear to be an independent risk for developing epilepsy.”
However, he cautioned that a prospective study with more rigorous data is required to get a more definitive answer to that question.
“Specifically, development of epilepsy would need to be precisely defined across all patients and monitored for extended periods of time to be sure all cases are captured,” he noted.
Sindhu and Goldenholz reported no relevant financial disclosures.
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