Sex Differences in Adverse Drug Reactions of Metformin: A Longitudinal Survey Study
Sex Differences in Adverse Drug Reactions of Metformin: A Longitudinal Survey Study
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DOI：
10.1007/s40264-020-00913-8
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发表时间：
2020-02-11
期刊：
影响因子：
4.2
通讯作者：
van Puijenbroek, Eugene P.
中科院分区：
文献类型：
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作者：
de Vries, Sieta T.;Denig, Petra;van Puijenbroek, Eugene P.
一般来说，女性比男性更经常经历二甲双胍相关的药物不良反应（ADR）。目的：我们旨在评估在开始治疗后的不同时间是否观察到二甲双胍报告的ADR的性别差异，并探索其与二甲双胍剂量随时间变化的性别差异的一致性。这可能会指导未来的研究，在评估二甲双胍相关的ADR的性别差异的机制，并可能指导性别特异性管理的ADR在临床实践中。方法本研究采用纵向设计，使用荷兰国家药物警戒中心Lareb通过其强化监测项目收集的开始二甲双胍治疗的患者数据。在开始后，要求患者完成基于网络的问卷六次（即，在2周、6周和3、6、9和12个月时）。结局变量为报告任何ADR的患者比例（主要）和二甲双胍剂量（次要）。每次评估时，分别使用Pearson卡方检验和Wilcoxon秩和检验检验ADR比例和剂量的性别差异。使用Bonferroni调整进行多重检验，p值< 0.01被认为具有统计学显著性。结果共纳入患者1712例，女性占40.9%。女性报告ADR的频率高于男性，在开始后2周（34% vs 25%，p < 0.001）和6周（37% vs 28%，p = 0.001）的评估中具有统计学显著性。一般而言，据报告，女性的处方剂量低于男性，这在9个月评估时具有统计学显著性（p < 0.01）。结论：在开始二甲双胍治疗后的第一周，报告的ADR存在性别差异，而在几个月后，观察到自我报告的处方剂量存在统计学显著差异。患者，特别是女性，可能会受益于在治疗开始时处方较低的二甲双胍剂量。
Introduction In general, women more often experience metformin-associated adverse drug reactions (ADRs) than men. Objectives We aimed to assess whether sex differences in reported ADRs for metformin are observed at different times after initiation, and to explore their concurrence with sex differences in the dose of metformin over time. This may guide future studies in assessing the involved mechanisms of sex differences in metformin-associated ADRs and may guide sex-specific management of ADRs in clinical practice. Methods This study has a longitudinal design using data about patients initiating metformin collected by the Dutch National Pharmacovigilance Center Lareb through their Intensive Monitoring program. Patients were asked to complete a web-based questionnaire six times after initiation (i.e., at 2 weeks, 6 weeks and at 3, 6, 9, and 12 months). The outcome variables were the proportion of patients reporting any ADR (primary) and the dose of metformin (secondary). Sex differences in the proportions of ADRs and in the dose were tested at each assessment using Pearson Chi-Squared tests and Wilcoxon rank-sum tests, respectively. Using Bonferroni adjustment for multiple testing, a p value < 0.01 was considered statistically significant. Results The number of included patients was 1712 (40.9% women). Women reported an ADR more often than men, which was statistically significant at the assessment at 2 weeks (34% vs 25%, p < 0.001), and 6 weeks (37% vs 28%, p = 0.001) after initiation. In general, women were reported to be prescribed a lower dose than men, which became statistically significant at the 9-month assessment (p < 0.01). Conclusions Sex differences in reported ADRs were seen in the first weeks after metformin initiation, whereas statistically significant differences in self-reported prescribed dosing were observed after several months. Patients, in particular women, might benefit from being prescribed lower metformin doses at treatment initiation.