Bezafibrate and simvastatin combination therapy for diabetic dyslipidaemia: efficacy and safety

Objective. To determine the efficacy and safety of a statin-fibrate combination in diabetes patients. Design. An open 21-month trial in which each patient first received the single drug for 6 months and then a combination of the two for 1 year. Setting. Three lipid clinics in university-based tertiary care hospitals. Patients. One hundred and forty-eight patients with type 2 (non-insulin-dependent, NIDDM) diabetes mellitus under stable control for 3 months by means of diet and oral hypoglycaemic medication. Intervention. Patients from one clinic (n = 48) received bezafibrate slow release (400 mg day(-1)), and patients from the other two clinics (n = 100) received simvastatin 20 mg day(-1). Six months later, all patients were switched to a daily combination of 400 mg bezafibrate slow release and 20 mg simvastatin for 1 year. Results. The combination of statin and fibrate led to a 23% reduction in total cholesterol, 42% reduction in triglycerides, 29% reduction in LDL-c, 25% increase in HDL-c, 10% decrease in fibrinogen and 19% reduction of Lp(a) levels, and a decrease in the cholesterol/HDL-c ratio (from 8.9 to 5.4) in all 148 patients. Cardiovascular (CV) event rate was significantly reduced from 9.5% during the first 6 months of the study to less than 2% during the last year of the study (whilst on combination Rx). Side-effects with all treatments included only two patients who developed myopathy when on the combined regimen and one on the single statin regimen. However, plasma creatinine phosphokinase (CPK) levels doubled (but remained within the normal range) in most of the patients on combination therapy, compared with only a mild increase in patients receiving a single medication. Conclusions. The statin and fibrate combination was found to be more efficacious than a single medication for treatment of diabetic dyslipidaemia, as evidenced by improvement in the lipoprotein profile, reductions in Lp(a), fibrinogen and CV event rate, and almost no clinically significant side-effects.