DEFINITION

• Elevated blood levels of lipids (cholesterol and triglycerides) and/or abnormalities in the blood concentrations of lipoproteins including: increased low-density lipoprotein cholesterol (LDL-C), decreased high-density lipoprotein cholesterol (HDL-C), and increased lipoprotein(a) (Lp(a)).

LDL-C

• Statins have been shown to reduce the risk of ischemic events in diabetes.[4][26]
• The reduction in cardiovascular (CV) events with statin therapy is directly related to the magnitude of LDL-C lowering, with every 39 mg/dl (1 mmol/l) resulting in an additional 22% reduction in CV events in type 2 diabetes.[9]
• Recently, the IMPROVE-IT trial showed addition of ezetimibe to statin therapy compared to placebo, in patients with acute coronary syndrome with an LDL-C level of 50-100 mg/dL on lipid-lowering therapy or LDL-C level of 50-125 mg/dL without therapy, had reduction in their LDL-C levels with improved CV outcomes. [9]
• Subgroup analysis revealed that among participants < 75 years of age, adding ezetimibe to simvastatin reduced the primary endpoint (CV death, major coronary event, or unstable angina) to a greater extent in patients with versus without diabetes. [6]
• In FOURIER and ODYSSEY trials, the addition of PCSK9 inhibitors to high-intensity statins reduced ischemic events in participants with atherosclerotic cardiovascular disease who were on statin therapy similarly in those with and without diabetes. [4][7][8][34][35]

Triglycerides

• Normal fasting triglyceride levels are < 150 mg/dL. Triglycerides >500 mg/dL are considered severe.
• Trials in triglycerides reduction in type 2 diabetes, with a fibrate alone [27] or in combination with a statin[18], did not show a significant reduction in cardiovascular mortality.
• The REDUCE-IT trial showed 4 gm of icosapent ethyl compared to placebo significantly reduced risk of ischemic events in those with hypertriglyceridemia (at LDL target) with benefit noted among individuals with and without diabetes. [5]

HDL

• HDL-C levels are considered low when < 40 mg/dL in men and < 50 mg/dL in women.
• In the AIM-HIGH trial (1/3 with diabetes), the addition of niacin to statin in patients with low HDL and high TG at baseline showed no benefit in a composite CV endpoint in participants with known CV disease (CVD), in both those with and without diabetes.[32]
• In the HPS2-THRIVE study (1/3 with diabetes), extended-release niacin in combination with statin therapy for secondary prevention led to reductions in LDL and increased HDL, with no reduction in major vascular events and increased serious adverse events related to glycemic control.[10]

Overall

• Primary and secondary prevention of CVD with statin therapy significantly reduces cardiovascular events and CV death in type 2 diabetes.