Background: Hypertriglyceridaemia (HTG), glucose intolerance, insulin resistance and elevated plasma activity of plasminogen activator inhibitor (PAI)-1 are risk factors for ischaemic heart disease. Because these conditions tend to cluster in the same individuals, the concerted action of gemfibrozil on all these parameters were investigated in a patient group with primary HTG.
Methods: Gemfibrozil was given as 600 mg tablets twice a day for 12 months to a group of middle-aged non-diabetic men with moderate HTG. Patients served as their own controls, because the treatment period was preceded by a single-blinded 2-month placebo phase. Gradient gel electrophoresis subfractionation of HDL was performed and glucose tolerance was defined according to World Health Organization criteria. The insulin sensitivity was assessed by the insulin-modified minimal model method. Plasma PAI-1 was assayed as activity.
Results: Serum triglyceride concentration was lowered by 49%. Serum high density lipoprotein (HDL) cholesterol concentration was raised by 11% with percentage shift towards the smaller HDL3c subfraction. The low-density lipoprotein cholesterol concentration remained unchanged. The proportion of glucose-intolerant subjects and insulin sensitivity were not altered by gemfibrozil. Plasma PAI-1 activity and fibrinogen levels were unaffected by gemfibrozil. The serum activity of gamma-glutamyltranspeptidase was lowered in all patients.
Conclusion: Gemfibrozil is safe and effective with regard to its serum triglyceride-lowering potential. However, glucose intolerance, insulin resistance and elevated plasma PAI-1 activity, frequently seen in HTG patients, are not to be expected to be normalized by this drug.