Gemfibrozil alone and in combination with lovastatin for treatment of hypertriglyceridemia in NIDDM

Hypertriglyceridemic patients with non-insulin-dependent diabetes mellitus (NIDDM) have an increased risk of coronary heart disease (CHD) and acute pancreatitis. To examine the potential of hypolipidemic drugs for therapy of lipoprotein abnormalities in NIDDM, 10 patients maintaining marked (plasma triglycerides >500 mg/dl) and 6 with moderate (plasma triglycerides 250-500 mg/dl) hypertriglyceridemia, despite good glycemic control, were studied in two phases. In the first phase, gemfibrozil alone (600 mg twice daily) was compared with a placebo, and in the second phase a combination of gemfibrozil and lovastatin (20 mg twice daily) was compared with gemfibrozil alone in a randomized, double-blind, placebo-controlled crossover study. In markedly hypertriglyceridemic patients, gemfibrozil reduced plasma triglycerides by 52% and very-low-density lipoprotein cholesterol (VLDL-chol) by 55% and increased high-density lipoprotein cholesterol by 23% compared with a placebo. However, low-density lipoprotein cholesterol (LDL-chol) levels increased (42%), and LDL apolipoprotein B (apoB) levels remained unchanged. Addition of lovastatin to gemfibrozil effectively reduced total cholesterol (25%), LDL-chol (30%), and LDL-apoB (19%). Lovastatin further reduced plasma triglycerides (11%) and VLDL-chol (27%). However, in moderately hypertriglyceridemic patients, gemfibrozil or the combination therapy did not seem to offer benefits over the previously reported study with lovastatin alone. Glycemic control was maintained throughout the study. In conclusion, the beneficial effects of the combination therapy on lipoprotein levels in markedly hypertriglyceridemic NIDDM patients could decrease the risk of development of both acute pancreatitis and CHD.