The risk of common hypoglycemic and antihypertensive medications and COVID-19: A 2-sample Mendelian randomization study.

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It has been reported that diabetes and hypertension increase the adverse outcomes of coronavirus disease 2019 (COVID-19). Aside from the inherent factors of diabetes and hypertension, it remains unclear whether antidiabetic or antihypertensive medications contribute to the increased adverse outcomes of COVID-19. The effect of commonly used antidiabetic and antihypertensive medications on COVID-19 outcomes has been inconsistently concluded in existing observational studies. Conducting a systematic study on the causal relationship between these medications and COVID-19 would be beneficial in guiding their use during the COVID-19 pandemic. We employed the 2-sample Mendelian randomization approach to assess the causal relationship between 5 commonly used antidiabetic medications (SGLT-2 inhibitors, Sulfonylureas, Insulin analogues, Thiazolidinediones, GLP-1 analogues) and 3 commonly used antihypertensive medications (calcium channel blockers [CCB], ACE inhibitors, β-receptor blockers [BB]), and COVID-19 susceptibility, hospitalization, and severe outcomes. The genetic variations in the drug targets of the 5 antidiabetic medications and 3 antihypertensive medications were utilized as instrumental variables. European population-specific genome-wide association analysis (GWAS) data on COVID-19 from the Host Genetics Initiative meta-analyses were obtained, including COVID-19 susceptibility (n = 2597,856), COVID-19 hospitalization (n = 2095,324), and COVID-19 severity (n = 1086,211). The random-effects inverse variance-weighted estimation method was employed as the primary assessment technique, with various sensitivity analyses conducted to evaluate heterogeneity and pleiotropy. There were no potential associations between the genetic variations in the drug targets of the 5 commonly used antidiabetic medications (SGLT-2 inhibitors, Sulfonylureas, Insulin analogues, Thiazolidinediones, GLP-1 analogues) and the 3 commonly used antihypertensive medications (CCBs, ACE inhibitors, BBs) with COVID-19 susceptibility, hospitalization, and severity (all P > .016). The findings from this comprehensive Mendelian randomization analysis suggest that there may be no causal relationship between the 5 commonly used antidiabetic medications (SGLT-2 inhibitors, Sulfonylureas, Insulin analogues, Thiazolidinediones, GLP-1 analogues) and the 3 commonly used antihypertensive medications (CCBs, ACE inhibitors, BBs) with COVID-19 susceptibility, hospitalization, and severity.