Lipid management to reduce cardiovascular risk in type 2 diabetes

Type 2 diabetes mellitus (T2DM) doubles the risk of atherosclerotic cardiovascular disease. The vast majority of this increased risk cannot be explained by the coexistence of conventional risk factors. In some people, T2DM and insulin resistance may increase the production of triglyceride-rich lipoproteins (TRLs). They contain apolipoprotein B100 (apoB100) and transport triglycerides (TG) and cholesterol esters, which can enter the arterial intima and induce atherosclerotic plaque formation. Thus, the cardiovascular risk is further increased (beyond the risk associated with T2DM alone). Current cardiovascular therapies in lipid management focus on lowering apoB-carrying lipoproteins and non-HDL-C (HDL: high-density lipoprotein; C: cholesterol) to reduce cardiovascular risk. In addition to statins and ezetimibe, there are also new approaches. These include bempedoic acid, a prodrug that acts by inhibiting the cholesterol synthesis pathway and increases the expression of low-density lipoprotein (LDL) receptors, and by targeting PCSK9 (PCSK9: proprotein convertase subtilisin/kexin type 9) via small interfering RNA (RNA: ribonucleic acid), and monoclonal antibodies that extend the life cycle of expressed LDL receptors. Both approaches lead to elimination of ApoB-containing lipoproteins. Most studies with omega-3 fatty acids found no additional cardiovascular benefit, with the exception of icosapent ethyl, which reduced cardiovascular events despite modest reductions in TG and TRL. In contrast, the cardiovascular benefit of fibrates has not been proven in current therapy. Because patients with T2DM are at higher absolute risk, lower lipid targets are usually recommended. Inevitably, these are difficult to achieve for most patients with monotherapy, so that combination therapy is required.