Pharmacologic treatment of type 2 diabetic dyslipidemia

Abstract

Patients with diabetes mellitus have a higher risk for cardiovascular heart disease (CHD) than does the general population, and once they develop CHD, mortality is higher. Good glycemic control will reduce CHD only modestly in patients with diabetes. Therefore, reduction in all cardiovascular risks such as dyslipidemia, hypertension, and smoking is warranted. The focus of this article is on therapy for dyslipidemia in patients with type 2 diabetes. Patients with the metabolic syndrome (insulin resistance) share similarities with patients with type 2 diabetes and may have a comparable cardiovascular risk profile. Diabetic patients tend to have higher triglyceride, lower high-density lipoprotein cholesterol (HDL), and similar low-density lipoprotein cholesterol (LDL) levels compared with those levels in nondiabetic patients. However, diabetic patients tend to have a higher concentration of small dense LDL particles, which are associated with higher CHD risk. Current recommendations are for an LDL goal of less than 100 mg/dl (an option of < 70 mg/dl in very high-risk patients), an HDL goal greater than 40 mg/dl for men and greater than 50 mg/dl for women, and a triglyceride goal less than 150 mg/dl. Nonpharmacologic interventions (diet and exercise) are first-line therapies and are used with pharmacologic therapy when necessary. Lowering LDL levels is the first priority in treating diabetic dyslipidemia. Statins are the first drug choice, followed by resins or ezetimibe, then fenofibrate or niacin. If a single agent is inadequate to achieve lipid goals, combinations of the preceding Drugs may be used. For elevated triglyceride levels, hyperglycemia must be controlled first. If triglyceride or HDL levels remain uncontrolled, pharmacologic agents should be considered. Fibrates are slightly more effective than niacin in lowering triglyceride levels, but niacin increases HDL levels appreciably more than do fibrates. Unlike gemfibrozil, niacin selectively increases subfraction Lp A-I, a cardioprotective HDL. Niacin is distinct in that it has a broad spectrum of beneficial effects on lipids and atherogenic lipoprotein subfraction levels. Niacin produces additive results when used in combination therapy. Recent data suggest that lower dosages and newer formulations of niacin can be used safely in diabetic patients with good glycemic control. Current evidence and guidelines mandate that diabetic dyslipidemia be treated aggressively, and lipid goals can be achieved in most patients with diabetes when all available products are considered and, if necessary, used in combination.