Mendelian randomization and pharmacovigilance analyses reveal the causal relationship between antidiabetic drugs and psychiatric disorders

Background Several studies have reported that antidiabetic drugs are associated with psychiatric disorders, but whether they have a causal relationship is unclear. The aim of this study was to explore the causal relationship between antidiabetic drugs and psychiatric disorders using two-sample Mendelian randomization (MR). Methods In this study, we used a two-sample Mendelian randomization approach to analyse the causal relationship between antidiabetic drugs and eight psychiatric disorders. The summary data for both exposure and outcomes were obtained from the Integrative Epidemiology Unit (IEU) online database. Inverse-variance-weighted (IVW) and wald ratio were used as the main analysis methods. Heterogeneity, horizontal pleiotropy test and leave-one-out method were used as sensitivity analyses. And finally we had a pharmacovigilance analysis. Results IVW method showed that sulfonylureas may be causally associated with the following three psychiatric disorders: bipolar disorder (OR = 2.55, 95% CI: 1.27–5.13, P = 0.008), anorexia nervosa (OR = 10.71, 95% CI: 1.20-95.54, P = 0.03), attention deficit hyperactivity disorder (ADHD) (OR = 5.21, 95% CI: 1.47–18.49, P = 0.01). Sulfonylureas pharmacovigilance analyses have also identified some signals of adverse effects in psychiatric disorders. Conclusion This study found some psychiatric adverse effects of sulfonylureas but more clinical trials and animal studies are needed to confirm this.