Effects of antidiabetic and antihyperlipidemic agents on C-reactive protein

Type 2 diabetes mellitus (DM) increases the risk of cardiovascular disease, a major cause of morbidity and mortality. Central to type 2 DM is insulin resistance, a proinflammatory, hypercoagulable state that predisposes patients to develop cardiovascular disease and that is associated with risk factors for atherosclerosis including dyslipidemia, hypertension, inflammation, and altered hemostasis. Atherosclerosis is recognized as a chronic inflammatory disease of the arteries. C-reactive protein (CRP) is an acute-phase response protein that is considered both a marker of inflammation and a predictor of cardiovascular events including myocardial infarction, stroke, peripheral arterial disease, and sudden cardiac death. Evidence indicates that CRP has a direct proatherogenic effect through up-regulation of angiotensin II type 1 receptors and through the stimulation of other proinflammatory factors. Patients with type 2 DM tend to have higher CRP concentrations than do those without it, suggesting an increased role of inflammation in the accelerated atherosclerosis seen in these patients. Reducing CRP concentrations through lifestyle changes or pharmacotherapeutics could have clinical benefit; long-term studies are needed to determine whether reductions in CRP concentrations translate into improved cardiovascular outcomes. Because glucose and lipid levels as well as CRP concentrations are often elevated in patients with type 2 DM, an agent that positively affects multiple cardiovascular risk factors would be most beneficial. This article reviews available data on antidiabetic and antihyperlipidemic agents that reduce CRP concentrations in addition to their primary effect of lowering glucose or lipid levels.