The Helsinki Heart Study of gemfibrozil demonstrated a 10% drop in total cholesterol, an 11% drop in LDL, a 35% drop in triglycerides, and an 11% increase in HDL. The Diabetes Atherosclerosis Intervention Study (DAIS) used fenofibrate therapy and measured the progress of atherosclerosis using angiography, documenting a 40% reduction in the progress of the disease.
Other triglyceride-lowering agents include fish oils that have high levels of omega-3 fatty acids. In addition to lowering triglycerides, omega-3 fatty acids also help reduce blood clotting and improve other facets of heart function. Flaxseed oil is also rich in omega-3 fatty acids and has the advantage of not having a fishy taste.
The role of diabetes drugs
There are a number of drugs that are often prescribed for people with diabetes for other purposes but which have some positive effect on lipids as well. Since people with diabetes may be taking these medicines anyway, Dr. Keilson feels they can be an important part of the management of dyslipidemia.
The thiazolidinediones (TZDs), rosiglitazone (Avandia) and pioglitazone (Actos), are used primarily to reduce the insulin resistance common in Type 2 diabetes. In people taking a TZD, the size of LDL particles increases, and HDL levels rise. Pioglitazone also lowers triglyceride levels, but rosiglitazone raises LDL levels.
The primary side effects of the TZDs are weight gain and fluid retention. The American Heart Association and the ADA have recommended caution in using them in people with congestive heart failure or risk factors for it and additionally recommend that they not be used in people with advanced congestive heart failure.
At higher doses, metformin (Glucophage, Glucophage XR) is able to reduce total cholesterol levels. Metformin is also linked to some weight loss, which can have a beneficial effect on lipids.
Acarbose (Precose) is used primarily to slow the absorption of complex starches in the intestine, helping to reduce high blood glucose levels after a meal. It also appears to lower LDL levels and raise HDL levels in the process. The evidence for lipid benefits from miglitol (Glyset), which is in the same drug class as acarbose, is inconclusive.
The anti-obesity drugs orlistat (Xenical) and sibutramine (Meridia) are primarily used for weight loss but may have positive effects on blood lipids as well. Orlistat blocks the enzymes that break down fat in food, preventing as much as 30% of the fat from being absorbed. Treatment with orlistat has produced statistically significant lowering of total cholesterol, LDL cholesterol, and triglycerides in a clinical trial.
Sibutramine works through the central nervous system to suppress appetite. The Sibutramine Trial of Obesity Reduction and Maintenance (STORM) found that in addition to its weight-loss benefits, sibutramine lowered levels of triglycerides and increased levels of HDL cholesterol.
Combination therapy
The complex dyslipidemia of diabetes often calls for a combination of drugs to achieve target levels of cholesterol. Most common are combinations of statins, which are effective for lowering LDL levels, with other drugs that address high triglycerides and low HDL levels.
“If you have a person with a low LDL level but who has high triglycerides and a low HDL level,” Dr. Keilson says, “you need to treat him differently than a person with high LDL levels. You can attempt to control his problem with more intensive blood sugar control, which will lower triglycerides, and with dietary modifications that reduce carbohydrates. After that, the next step would be to add a fibrate, fish oil or flaxseed oil, or niacin. The addition of ezetimibe to statin therapy may be especially helpful in raising HDL levels.”
