Exploring the Therapeutic Potential of Antidiabetic Drugs in Cardiac Arrhythmia Management: A Drug Target Mendelian Randomization Study

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Abstract
Background: Cardiac arrhythmias pose a major health concern while the role of antidiabetic medications in cardiac arrhythmic risks is not fully understood. Method: We conducted a two‐sample Mendelian Randomization (MR) analysis using genetic instruments extracted from hemoglobin A1C (HbA1c) as proxies for antidiabetic drug targets to evaluate their causal relationship with five cardiac arrhythmias derived from the Finngen database. Summary‐data‐based Mendelian randomization (SMR) utilizing gene expression data from the eQTLgen consortium was further employed to assess the role of antidiabetic drug targets in cardiac arrhythmias from the gene expression perspective. Results: Three significant associations were identified. Sulfonylurea targets KCNJ11/ABCC8 were associated with a decreased incidence of paroxysmal tachycardia (OR: 0.69, 95% CI: 0.56, 0.86, P FDR = 0.022). Sodium‐glucose cotransporter 2 inhibitor (SGLT2i) target SLC5A2 was linked to a reduced risk of right bundle branch block (OR: 0.85, 95% CI: 0.77, 0.94, PFDR = 0.022), and thiazolidinediones (TZDs) targeting RXRB were associated with a lowered atrial fibrillation occurrence (OR: 0.88, 95% CI: 0.82, 0.94, P FDR = 0.019). No significant relationships were found between any antidiabetic drug targets and left bundle branch block or atrioventricular block. SMR analysis indicated that lowered expression of KCNJ11 was related to a decreased paroxysmal tachycardia risk (OR: 1.05, 95% CI: 1.01, 1.08, P SMR = 0.010), further confirming the role of KCNJ11 in paroxysmal tachycardia. Conclusion: Our findings suggest that several antidiabetic drug targets may have potential therapeutic applications in the management of cardiac arrhythmias.
Funding Information
  • National Natural Science Foundation of China (81900229)

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