EFFICACY AND SAFETY OF FLUVASTATIN IN PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS AND HYPERLIPIDEMIA

The purpose of this study was to investigate the triglyceride-lowering effect of fluvastatin, a new 3-hydroxy-3-methylglutaryl-coenzyme A (H MG-CoA) reductase inhibitor, in the combined hyperlipidemia of non-ins ulin-dependent diabetes mellitus (NIDDM). In this double-blind trial, 66 patients with NIDDM (24 men and 42 women, age 37-71), with low-dens ity lipoprotein cholesterol (LDL-C) levels of 130-300 mg/dL (3.4-7.8 m mol/L) and triglyceride (TG) levels of 200-1,000 mg/dL (2.3-11.3 mmol/ L) despite an 8-week period of diet modification, were randomized to r eceive either fluvastatin at 20 mg once daily (at night) or placebo fo r 6 weeks, followed by an increase of fluvastatin to 20 mg twice daily for an additional 6 weeks of treatment. After 12 weeks, fluvastatin d ecreased plasma levels of total cholesterol by 19.9% (p < 0.001), LDL- C by 24.3% (p < 0.001), TG by 15.3% (p < 0.01), very low-density lipop rotein cholesterol (VLDL-C) by 19.7% (p < 0.001), apolipoprotein (apo) B by 21.3% (p < 0.001), and apo E by 18.1% (p < 0.05), whereas high-d ensity lipoprotein cholesterol (HDL-C) levels were increased by 4.6% ( p < 0.05). Within the intermediate-density lipoprotein cholesterol (ID L-C) fraction, a constituent analysis revealed a total cholesterol red uction of 35% (p < 0.01). Greater decreases in TG were seen in patient s who had higher levels of TG at baseline. Slight increases in glycemi c indices and body weight were seen in both treatment groups. The occu rrence of clinical and laboratory abnormalities was similar with both active treatment and placebo, and no myositis was observed. Slight inc reases in aspartate (ASAT; mean 5.6 U/L at the higher dose) and alanin e (ALAT; mean 5.1 U/L at the higher dose) aminotransferases were not c linically significant. In this first, parallel-group placebo-controlle d trial of a reductase inhibitor in a free-living NIDDM population, fl uvastatin safely improved the combined TG, VLDL-C, LDL-C, LDL-C, and H DL-C abnormalities associated with NIDDM.-