Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts.
Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
JAMA Netw Open. 2022 Apr 1;5(4):e226484. doi: 10.1001/jamanetworkopen.2022.6484.
Anticonvulsant mood stabilizer treatment is associated with an increased risk of weight gain, but little is known about the risk of developing type 2 diabetes (T2D).
To evaluate the comparative safety of anticonvulsant mood stabilizers on risk of T2D in adults and children by emulating a target trial.
DESIGN, SETTING, AND PARTICIPANTS: This observational cohort study used data from IBM MarketScan (2010-2019), with a 5-year follow-up period. The nationwide sample of US commercially insured patients included children (aged 10-19 years) and adults (aged 20-65 years) who initiated anticonvulsant mood stabilizer treatment. Data were analyzed from August 2020 to May 2021.
Initiation and continuation of carbamazepine, lamotrigine, oxcarbazepine, or valproate.
Onset of T2D during follow-up. Weighted pooled logistic regression was used to estimate the association of initiation and continuation of carbamazepine, lamotrigine, oxcarbazepine, or valproate with the risk of developing T2D. Inverse probability weights were used to control for confounding and loss to follow-up by measured baseline and time-varying covariates.
The analysis included 274 206 adults (159 428 women [58%]; mean [SD] age, 39.9 [13.2] years) and 74 005 children (38 672 girls [52%]; mean [SD] age, 15.6 [2.6] years) who initiated an anticonvulsant mood stabilizer. 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% to 1.76%). The number needed to harm was 87 patients initiating valproate for 1 patient to develop T2D within 5 years compared with initiation of lamotrigine. Point estimates were similar when evaluating the association of treatment continuation (5-year RD, 1.99%; 95% CI, -0.64% to 5.31%). The estimated association was smaller and more variable comparing carbamazepine and oxcarbazepine to lamotrigine. In children, RDs were much smaller and more variable (5-year RD for initiation of oxcarbazepine vs lamotrigine, 0.29%; 95% CI, -0.12% to 0.69%; 5-year RD for initiation of valproate vs lamotrigine, 0.18%; 95% CI, -0.09% to 0.49%).
In this cohort study, valproate was associated with the highest risk of developing T2D in adults. 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.
抗惊厥情绪稳定剂治疗与体重增加风险增加有关，但人们对 2 型糖尿病（T2D）发展风险知之甚少。
通过模拟目标试验，评估抗惊厥情绪稳定剂在成人和儿童中治疗 T2D 的相对安全性。
设计、设置和参与者：这项观察性队列研究使用了 IBM MarketScan（2010-2019 年）的数据，随访期为 5 年。该研究的全国性美国商业保险患者样本包括接受抗惊厥情绪稳定剂治疗的儿童（年龄 10-19 岁）和成人（年龄 20-65 岁）。数据于 2020 年 8 月至 2021 年 5 月进行分析。
卡马西平、拉莫三嗪、奥卡西平或丙戊酸的起始和持续使用。
随访期间 T2D 的发病情况。加权汇总逻辑回归用于估计卡马西平、拉莫三嗪、奥卡西平和丙戊酸的起始和持续使用与 T2D 发病风险之间的关联。使用逆概率权重来控制基于基线和随时间变化的混杂因素以及随访丢失的影响。
分析包括 274206 名成年人（159428 名女性[58%]；平均[SD]年龄，39.9[13.2]岁）和 74005 名儿童（38672 名女孩[52%]；平均[SD]年龄，15.6[2.6]岁）开始接受抗惊厥情绪稳定剂治疗。在成年人中，与拉莫三嗪相比，丙戊酸的起始治疗与 T2D 发病风险增加相关（5 年风险差异[RD]，1.17%；95%CI，0.66%至 1.76%）。与起始拉莫三嗪相比，需要 87 名患者起始丙戊酸治疗才能在 5 年内有 1 名患者患上 T2D。当评估治疗持续时间的关联时，点估计值相似（5 年 RD，1.99%；95%CI，-0.64%至 5.31%）。与拉莫三嗪相比，比较卡马西平和奥卡西平的估计关联较小且更具变异性。在儿童中，RD 更小且更具变异性（与拉莫三嗪相比，奥卡西平起始治疗的 5 年 RD 为 0.29%；95%CI，-0.12%至 0.69%；与拉莫三嗪相比，丙戊酸起始治疗的 5 年 RD 为 0.18%；95%CI，-0.09%至 0.49%）。
在这项队列研究中，丙戊酸与成年人 T2D 发病风险的相关性最高。在儿童中，相对安全性通常相似，但估计值较小且变异性较大。在没有随机试验的情况下，在医疗保健数据库中模拟目标试验可以生成特定年龄的药物安全性数据，以辅助治疗决策。
