We show that FXR activation by Fexaramine (Fex) together with BRD4 inhibition by JQ1 synergistically suppressed IL-1β-induced inflammation while also improving β cell identity and insulin secretion in both <i>db/db</i> model and high-fat diet (HFD) plus multi low-dose streptozotocin (MLD-STZ) model of diabetes. The gene discussed is BRD4; the disease is diabetes mellitus.