Valproate has highest diabetes risk among anticonvulsant mood stabilizers: JAMA

USA: Valproate is linked to the highest risk of acquiring type 2 diabetes (T2D) in adults, according to recent cohort research published in the Journal of the American Medical Association.

Treatment with anticonvulsant mood stabilizers is linked to an increased risk of weight gain, but less is known regarding the risk of acquiring T2D. Jenny W. Sun and colleagues conducted this investigation to assess the comparative safety of anticonvulsant mood stabilizers on the risk of T2D in adults and children using an emulation of a target trial.

This observational cohort research employed IBM Market Scan data from 2010 to 2019, with a 5-year follow-up period. Children (aged 10-19 years) and adults (aged 20-65 years) were included in the countrywide sample of commercially insured patients who began anticonvulsant mood stabilizer therapy. The data was examined from August 2020 to May 2021. This research enrolled patients who had begun and continued to take carbamazepine, oxcarbazepine, lamotrigine, or valproate. The major consequence was the onset of T2D during the follow-up period. The researchers utilized weighted pooled logistic regression to determine the relationship between starting and continuing carbamazepine, oxcarbazepine, lamotrigine, or valproate with the likelihood of developing T2D. To account for confounding and loss to follow-up caused by observed baseline and time-varying factors, inverse probability weights were applied.

The findings of this study were as follows:

1. The study comprised 274 206 adults and 74 005 children who had started using an anticonvulsant mood stabilizer.

2. In adults, starting valproate was associated with a higher chance of developing T2D than starting lamotrigine.

3. When compared to starting lamotrigine, the number of patients needed to harm was 87 when starting valproate for 1 patient to develop T2D within 5 years.

4. When analyzing the relationship of treatment continuation, point estimates were comparable.

5. When carbamazepine and oxcarbazepine were compared to lamotrigine, the estimated relationship was lower and more variable.

6. RDs were substantially smaller and more varied in children.

In conclusion, these data suggest that, at the population level, the decision of which anticonvulsant mood stabilizer to begin may have significant links with the occurrence of T2D. Patients and doctors worried about the possible metabolic side effects of therapy may consider starting with lamotrigine, which has been linked to the lowest risk of T2D.

Reference: Sun JW, Young JG, Sarvet AL, et al. Comparison of Rates of Type 2 Diabetes in Adults and Children Treated With Anticonvulsant Mood Stabilizers. JAMA Netw Open. 2022;5(4):e226484. doi:10.1001/jamanetworkopen.2022.6484