Beyond Blood Sugar: Ozempic May Reduce The Risk of Epilepsy

People with type 2 diabetes have a higher risk of developing epilepsy over their lifetime. This large study with data from real patients showed that a specific type of diabetes medication, glucagon-like peptide-1 receptor agonists, is associated with a lower risk of developing epilepsy compared to another common treatment. The protective effect was observed from the first year of use and was maintained over time. These results suggest that some diabetes medications may also protect the brain, going beyond blood sugar control.

Type 2 diabetes mellitus is a very common chronic disease characterized by consistently high blood sugar levels. In addition to affecting organs such as the heart, kidneys, and eyes, diabetes also has significant impacts on the brain. People with type 2 diabetes have a higher risk of developing neurological problems, including cognitive impairment, dementia, and epilepsy.

Epilepsy is a neurological condition marked by recurrent seizures caused by abnormal electrical discharges in the brain. Although often associated with childhood, epilepsy can also occur in adulthood, especially in people with metabolic and vascular diseases, such as diabetes.

In recent years, some medications used to treat type 2 diabetes have attracted attention not only for helping to control blood glucose, but also for possible beneficial effects on the brain. Among them are the so-called glucagon-like peptide-1 receptor agonists (Ozempic), a class of medications that mimics the action of a natural hormone in the intestine.

This hormone helps regulate blood sugar, reduces appetite, and improves the body's response to insulin. Studies in animals and in the laboratory have suggested that these medications could also protect neurons, reduce brain inflammation, and improve the functioning of the nervous system.

However, there was still little evidence in real people, in the clinical world, about whether these medications could reduce the risk of neurological diseases, such as epilepsy.

To investigate this question, researchers conducted a large observational study using an international database called TriNetX, which gathers health information from millions of patients. Data collected between 2015 and 2023 from adults aged eighteen or older diagnosed with type 2 diabetes were analyzed.

The researchers compared two groups of people: those who started treatment with glucagon-like peptide-1 receptor agonists (Ozempic) and those who started using another class of diabetes medications, dipeptidyl peptidase-4 inhibitors (vildagliptin and sitagliptin), which also act on glucose metabolism, but through a different mechanism and without clear evidence of direct action on the brain.

To ensure a fair comparison, people who already had epilepsy, previous seizures, or who used anticonvulsant medications were excluded from the study. In addition, the researchers applied a statistical technique called propensity score matching, which essentially creates two very similar groups based on important characteristics such as age, sex, associated health conditions, body weight, socioeconomic level, and use of other medications.

In this way, the main difference between the groups was the type of diabetes medication used, increasing confidence that the observed results are related to this therapeutic choice.

After this matching, more than 450,000 patients were included, with approximately 226,000 people in each group. The average age was just over 70 years, and almost half of the participants were female. During the follow-up period, the researchers analyzed how many people in each group developed epilepsy, identified by standardized medical records.

The results showed that epilepsy was slightly less frequent among people who used Ozempic. Although the absolute difference seems small, it was statistically significant and consistent over time.

In practical terms, this means that the use of this type of medication was associated with a real reduction in the risk of developing epilepsy when compared to other diabetes treatments. This protection was observed as early as the first year of use and was maintained after three and five years of follow-up.

Among the different medications in this class, one in particular, semaglutide, showed the strongest association with a reduced risk of epilepsy. This suggests that, in addition to the effect of the class as a whole, some specific drugs may offer even more pronounced neurological benefits. Importantly, this protective association was observed in different subgroups of the population, including men and women and different age ranges, which reinforces the robustness of the findings.

The researchers also performed additional analyses to ensure that the results were not explained by external factors, such as people who switched medications or used more than one type over time. Even after these more rigorous analyses, the results remained virtually the same, increasing confidence that the observed association is consistent.

In the discussion, the authors highlight that these findings reinforce the hypothesis that glucagon-like peptide-1 receptor agonists may offer benefits to the brain that go beyond blood sugar control.

Possible mechanisms include reduced brain inflammation, improved neuronal energy metabolism, protection against vascular damage, and modulation of brain electrical activity.

However, as this is an observational study, it is not possible to state with certainty that these medications directly reduce the risk of epilepsy. Even so, the results are highly suggestive and point to a potentially clinically relevant neuroprotective effect.

READ MORE:

Association Between GLP-1 Receptor Agonist Use and Epilepsy Risk in Type 2 Diabetes

Ching-Yang Cheng, Shih-Chang Lo, Chien-Ning Huang, Yi-Sun Yang, Yu-Hsun Wang, and Edy Kornelius

Neurology. January 13, 2026 issue 106 (1) e214509DOI: 10.1212/WNL.0000000000214509

Abstract:

Individuals with type 2 diabetes mellitus (T2DM) are at an increased risk of developing epilepsy, particularly in later life. While preclinical studies suggest neuroprotective properties of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), real-world comparative effectiveness data remain limited. We aimed to evaluate whether GLP-1 RA use is associated with a lower risk of incident epilepsy compared with dipeptidyl peptidase-4 inhibitor (DPP-4i) use in adults with T2DM. We conducted a retrospective cohort study using the TriNetX network from 2015 to 2023, including adults aged 18 years or older with T2DM who were new users of either GLP-1 RAs or DPP-4is. Patients with a previous diagnosis of epilepsy or seizure, or those using antiepileptic drugs, were excluded. The primary outcome was incident epilepsy, identified using ICD-10-CM codes. Propensity score matching (1:1) was performed based on demographics, socioeconomic status, body mass index, comorbidities, and baseline medications. Cox proportional hazard models estimated hazard ratios (HRs) with 95% CIs. We also conducted prespecified subgroup and sensitivity analyses to assess the robustness of the findings. After matching, 452,766 patients were included (226,383 in each group; mean age 60.5 years; 47.1% female). During follow-up, 1,670 individuals in the GLP-1 RA group and 1,886 in the DPP-4i group developed epilepsy, corresponding to cumulative incidences of 2.35% vs 2.41%. GLP-1 RA use was associated with a significantly lower risk of epilepsy (HR 0.84, 95% CI 0.78–0.90), with protective associations evident at 1 year (HR 0.71, 95% CI 0.62–0.80), 3 years (HR 0.81, 95% CI 0.74–0.88), and 5 years (HR 0.82, 95% CI 0.76–0.88). Among individual agents, semaglutide showed the strongest association (HR 0.68, 95% CI 0.60–0.77). The results were consistent across major subgroups, including both age and sex. Sensitivity analyses excluding patients with overlapping or switching exposure yielded similar findings (HR 0.71, 95% CI 0.64–0.78). GLP-1 RA therapy was associated with a significantly lower epilepsy risk compared with DPP-4i use in adults with T2DM. These results support the hypothesis that GLP-1 RAs may exert neurologic benefits beyond glycemic control. Limitations include the observational design and potential residual confounding. This study provides Class III evidence that the use of GLP-1 RAs in people with T2DM results in a lower risk of developing epilepsy compared with those treated with DPP-4i.