Boston—Choosing one anticonvulsant mood stabilizer over another can make a meaningful difference in increasing the risk of T2D, according to a new study.

Anticonvulsant mood stabilizers are among the long-term medications suspected of increasing T2D risk, but little research has been conducted on differential risk of T2D associated with specific medications in this class. A recent cohort study published in the Journal of the American Medical Association Network Open involving 274,206 adults and 74,005 children provides an answer to the question of which drugs present the greatest risks.

Researchers from Harvard Medical School and Harvard Pilgrim Health determined that valproate was associated with the greatest risk of developing T2D in adults and calculated that the number needed to harm was 87 patients initiating valproate for one patient to develop T2D within 5 years compared with initiation of lamotrigine.

The findings were similar in children but less precise, the authors pointed out.

"The choice of which anticonvulsant mood stabilizer to initiate may be associated with meaningful reductions in T2D incidence, and patients and clinicians concerned about the potential metabolic adverse effects could consider initiating lamotrigine," the study advised.

While it is well known that anticonvulsant mood stabilizer treatment is associated with an increased risk of weight gain, less is understood about the therapy's link to the development of T2D, according to the authors. That is why they sought to evaluate the comparative safety of anticonvulsant mood stabilizers on the risk of T2D in adults and children.

Their observational cohort study used data from IBM MarketScan (2010-2019), with a 5-year follow-up period. It focused on a nationwide sample of U.S. commercially insured patients including children (aged 10-19 years) and adults (aged 20-65 years) who started anticonvulsant mood-stabilizer treatment. Analysis of data occurred from August 2020 to May 2021.

The study team evaluated initiation and continuation of carbamazepine, lamotrigine, oxcarbazepine, or valproate and any associated risks of developing T2D. The adults were 58% female with a mean age of 39.9 years, while the children were 52% girls with a mean age of 15.6 years.

Results indicated that, in adults, initiation of valproate was associated with an increased risk of developing T2D compared with initiation of lamotrigine (5-year risk difference [RD], 1.17%; 95% CI, 0.66%-1.76%). Researchers noted that the estimated association was smaller and more variable comparing carbamazepine and oxcarbazepine to lamotrigine.

In children, meanwhile, risk differences were much smaller and more variable (5-year RD for initiation of oxcarbazepine vs. lamotrigine, -0.29%; 95% CI, -0.12%-0.69%; 5-year RD for initiation of valproate vs. lamotrigine, 0.18%; 95% CI, -0.09%-0.49%), they added.

"In this cohort study, valproate was associated with the highest risk of developing T2D in adults," the authors concluded. "The comparative safety was generally similar in children, but estimates were small and variable. In the absence of randomized trials, emulating target trials within health care databases can generate the age-specific drug safety data needed to inform treatment decision-making."

Background information in the article advises that anticonvulsant mood stabilizers are widely used by adults and children for the treatment of epilepsy, bipolar disorder, and neuropathic pain.

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