Sodium-glucose cotransporter 2 inhibitors were associated with lower risks of late-onset epilepsy, status epilepticus, and initiation of antiseizure medications compared with dipeptidyl peptidase-4 inhibitors among patients aged 60 years and older with type 2 diabetes, although causality cannot be established due to the observational study design.
In a real-world cohort study using the TriNetX global network, researchers identified more than 1.4 million patients and, following propensity score matching, analyzed 60,203 patients in each treatment group with balanced baseline characteristics.
Over 3 years of follow-up, patients receiving sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) had a lower incidence of late-onset epilepsy compared with those receiving dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) (0.20% vs 0.42%), corresponding to a 45% lower risk.
SGLT2 inhibitor use was also associated with lower rates of status epilepticus (0.02% vs 0.07%; 62% lower risk) and initiation of antiseizure medications (1.33% vs 2.33%; 37% lower risk).
Cumulative incidence curves diverged early between groups, with statistically significant differences observed throughout follow-up.
Subgroup analyses showed lower risks of late-onset epilepsy and antiseizure medication initiation across patient demographics and comorbidities. For status epilepticus, statistically significant differences were observed only among patients aged 80 years and older, women, and patients with hypertension.
Among high-risk populations, SGLT2 inhibitor use was associated with lower risk of late-onset epilepsy in patients with prior stroke (1.20% vs 1.84%) and dementia (0.84% vs 2.26%), but not in those with traumatic brain injury or brain tumors.
Across sensitivity analyses varying follow-up intervals, prescription frequency, treatment duration, and comparator therapies, findings were generally consistent in direction across analyses. SGLT2 inhibitor use was also associated with lower likelihood of initiating highly specific antiseizure medications and lower electroencephalography utilization.
In secondary analyses of patients with preexisting epilepsy, SGLT2 inhibitor use was associated with numerically lower risks of dementia and psychiatric disorders. No statistically significant differences were observed in decline in activities of daily living, falls, or all-cause mortality.
The researchers noted several limitations, including reliance on coded diagnoses to identify epilepsy, lack of data on medication dosing and adherence, and the possibility of residual confounding. The data set also did not include detailed neurologic information such as neuroimaging or electrophysiologic measures.
“SGLT2 inhibitor use was associated with approximately 45% lower risk of late-onset epilepsy, 62% lower risk of status epilepticus, and 37% lower risk of antiseizure medication initiation,” wrote lead study researcher Bing-Hua Lin of Taipei Medical University in Taiwan, and colleagues.
The researchers reported no conflicts of interest.
Source: Epilepsia