Comparison of Rates of Type 2 Diabetes in Adults and Children Treated With Anticonvulsant Mood Stabilizers.
Comparison of Rates of Type 2 Diabetes in Adults and Children Treated With Anticonvulsant Mood Stabilizers.
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DOI：
10.1001/jamanetworkopen.2022.6484
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发表时间：
2022-04-01
影响因子：
13.8
通讯作者：
Block JP
中科院分区：
文献类型：
--
作者：
Sun JW;Young JG;Sarvet AL;Bailey LC;Heerman WJ;Janicke DM;Lin PD;Toh S;Block JP
这项队列研究使用了美国全国商业保险患者样本的数据，评估了抗惊厥情绪稳定剂与成人和儿童2型糖尿病发病率之间的关系。抗惊厥情绪稳定剂的治疗是否会增加2型糖尿病(T2D)的风险？在这项对274名 206名成人和74名 005名儿童进行的队列研究中，丙戊酸盐与成人发生T2D的风险最高相关，与开始服用拉莫三嗪的患者相比，在5年内开始服用丙戊酸盐的患者中，有87名患者需要伤害才能发展为T2D。在儿童中，研究结果大体上相似，但不那么精确。选择使用哪种抗惊厥药物可能会显著降低T2D的发生率，担心潜在代谢不良反应的患者和临床医生可以考虑使用拉莫三嗪。抗惊厥情绪稳定剂治疗与体重增加的风险有关，但对患2型糖尿病(T2D)的风险知之甚少。通过模拟靶点试验，评价抗惊厥情绪稳定剂对成人和儿童T2D风险的相对安全性。这项观察性队列研究使用了IBM MarketScan(2010-2019)的数据，并进行了5年的随访期。美国商业保险患者的全国样本包括开始抗惊厥情绪稳定剂治疗的儿童(10-19岁)和成年人(20-65岁)。对2020年8月至2021年5月的数据进行了分析。卡马西平、拉莫三嗪、奥卡西平或丙戊酸酯的起始和持续。在随访期内出现T2D。采用加权混合Logistic回归方法评估卡马西平、拉莫三嗪、奥卡西平或丙戊酸盐的开始和持续使用与发生T2D的风险之间的关系。通过测量的基线和随时间变化的协变量，使用逆概率权重来控制混杂和随访损失。分析包括274名 206成人(159名 428名女性(58%)；平均[SD]年龄39.9[13.2]岁)和74名 005儿童(38名 672名女孩[52%]；平均[SD]年龄15.6[2.6]岁)，他们服用了抗惊厥情绪稳定剂。在成人中，开始服用丙戊酸盐与开始服用拉莫三嗪相比，发生T2D的风险增加(5年风险差异[RD]，1.17%；95%CI，0.66%至1.76%)。与使用拉莫三嗪相比，5年内使用丙戊酸酯的87例患者中有1例发展为T2D，需要伤害的人数为87人。在评估持续治疗的关联性时，积分估计值相似(5年RD，1.99%；95%CI，−0.64%至5.31%)。卡马西平和奥卡西平与拉莫三嗪相比，估计的相关性较小，变异性较大。在儿童中，RDS要小得多，变异性也更大(奥卡西平与拉莫三嗪开始治疗的5年RD，0.29%；95%CI，−0.12%~0.69%；丙戊酸酯开始治疗5年RD，0.18%；95%CI，−0.09%~0.49%)。在这项队列研究中，丙戊酸盐与成人发生T2D的风险最高相关。儿童的相对安全性大体上是相似的，但估计值很小，而且变化很大。在没有随机试验的情况下，在卫生保健数据库中模拟目标试验可以生成为治疗决策提供信息所需的特定年龄段的药物安全性数据。
This cohort study evaluates the association between anticonvulsant mood stabiliziers and rates of type 2 diabetes in adults and children using data from a nationwide sample of US commercially insured patients. Is treatment with anticonvulsant mood stabilizers associated with an increased risk of type 2 diabetes (T2D)? In this cohort study of 274 206 adults and 74 005 children, valproate was associated with the highest risk of developing T2D in adults, with a number needed to harm of 87 patients initiating valproate for 1 patient to develop T2D within 5 years compared with initiation of lamotrigine. In children, findings were generally similar but less precise. 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. 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. 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.
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影响因子：
33.9
作者：
Divers, Jasmin;Mayer-Davis, Elizabeth J.;Wagenknecht, Lynne E.
通讯作者：
Wagenknecht, Lynne E.
影响因子：
2
作者：
Austin PC
通讯作者：
Austin PC
影响因子：
2.9
作者：
Egunsola O;Choonara I;Sammons HM
通讯作者：
Sammons HM
影响因子：
13.6
作者：
Garcia-Albeniz, Xabier;Hsu, John;Hernan, Miguel A.
通讯作者：
Hernan, Miguel A.
影响因子：
5
作者：
Cole, Stephen R.;Hernan, Miguel A.
通讯作者：
Hernan, Miguel A.