CYP3A4 and type 2 diabetes mellitus: Given that CYP3A4 metabolizes nearly 40% of therapeutic agents, reduced activity in T2D patients, shown by a 1.6-fold decrease in hepatic CYP3A4 levels and substrate metabolism, underscores the importance of caution with polypharmacy, as disease–drug–drug interactions may occur (Coutant and Hall, 2018).