The objective of this study was to compare the lipid-altering efficacy and safety of simvastatin with that of gemfibrozil in hypercholesterolemic patients with non-insulin-dependent diabetes mellitus (NIDDM). The study was a 24-week, double-blind, randomized, multicenter trial conducted at clinics and hospitals in the United States, Austria, Germany, Brazil, and New Zealand. The study population included 168 men and women aged 34 to 78 years with NIDDM and primary hyperholesterolemia (low-density lipoprotein cholesterol [LDL-C] level at screening was ≥4.9 mmol/L with no other risk factor or ≥4.1 mmol/L with one or more other risk factors). All patients had been under moderate-to-good diabetic control (hemoglobin A1c [HbA1c] ≤10.0%) for at least 6 months with diet alone, oral hypoglycemic agents, or insulin therapy. Patients meeting eligibility criteria were randomized to receive either simvastatin 10 mg (titrated up to 40 mg to achieve an LDL-C level <3.4 mmol/L) once in the evening or gemfibrozil 600 mg twice daily. There were 81 patients in the simvastatin group and 87 patients in the gemfibrozil group. After 17 weeks of treatment, simvastatin significantly reduced levels of total cholesterol, LDL-C, and very-low-density lipoprotein cholesterol (VLDL-C) by approximately 25%, 33%, and 20%, respectively (P ≤ 0.001), and triglycerides by about 9% (P ≤ 0.05). The drug increased high-density lipoprotein cholesterol (HDL-C) levels by about 6% (P < 0.01). Gemfibrozil significantly reduced total cholesterol, VLDL-C, and triglyceride levels by approximately 8%, 38%, and 27%, respectively (P < 0.001); it significantly increased HDL-C values by about 12% (P < 0.001). Gemfibrozil lowered LDL-C levels by 4% but not significantly. The decreases in total cholesterol and LDL-C were significantly greater (P < 0.001) in the simvastatin group, and decreases in VLDL-C and triglycerides were significantly greater in the gemfibrozil group (P < 0.01). The changes in HDL-C were not significantly different between groups. LDL-C values of <3.4 mmol/L were achieved in 60% of the simvastatin patients and 14% of the gemfibrozil patients. There were no significant between-group differences in fasting serum glucose or HbA1c at any time point. Glycemic profiles (performed at baseline and after 17 weeks of treatment) and glucose area under the curve (at baseline and after 17 weeks of treatment) were not significantly different between treatment groups. Both drugs were generally well tolerated. In conclusion, simvastatin was more effective in reducing total cholesterol and LDL-C levels, whereas gemfibrozil was more effective in reducing VLDL-C and triglyceride levels. There was no deterioration of glycemic control in patients treated with simvastatin.
ASJC Scopus subject areas
- Pharmacology (medical)