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A group of 14 diabetic patients was treated with gemfibrozil during a variable length of time ranging from nine to 23 weeks in order to establish if a lowering effect on the cholesterol and triglyceride levels could be achieved, as it had been in the case of another group of non-diabetic patients. The present results showed that: (1) The drug is remarkably well tolerated. (2) With doses ranging between 400 and 800 mg per day the magnitude of the effect of the drug was less than that observed in our previous trial with non-diabetic subjects. The effect upon triglycerides seemed to be reduced more than that upon cholesterol when compared with results in higher-dose studies. (3) In this group of diabetic patients (3 insulin dependent, 11 maturity-onset type) control of the diabetic condition was never impaired and appeared in some cases to be slightly improved by gemfibrozil. (4) There was no evidence of undesirable interaction with any of the anti-diabetic drugs used.

During treatment with gemfibrozil, 1200 mg daily, total serum triglyceride levels were reduced in 7 of the 11 patients, owing chiefly to a fall in VLDL triglyceride levels. Total serum cholesterol responded variably, falling in a majority of patients with hypercholesterolaemia. High density lipoprotein cholesterol rose during treatment in patients who had either hypertriglyceridaemia or hypercholesterolaemia.

Gemfibrozil was found to be an effective hypotriglyceridaemic agent in types IV, IIb and V hyperlipoproteinaemia. When given at a dose level of 800 mg/day its activity was nearly of the same order of magnitude as 1.5 g/day of clofibrate.

The efficacy of gemfibrozil in lowering increased serum lipoprotein concentrations was tested in a placebo-controlled cross-over trial on 30 patients. Administered in a dose of 1200 mg daily, gemfibrozil reduced increased serum triglyceride levels by approximately 50% and reduced increased serum cholesterol concentrations by about 20%. Elevated VLDL triglyceride levels were reduced by 60%, and increased LDL cholesterol concentrations were reduced by approximately 20%. The mean HDL cholesterol concentration increased during gemfibrozil treatment. No adverse reactions attributable to gemfibrozil were recorded during the trial.

The efficacy of gemfibrozil as a hypolipidaemic agent was compared with that of clofibrate in a cohort of 80 subjects, half being treated with gemfibrozil and half with clofibrate. The majority of the subjects were either of the type IIa or IIb. Both drugs proved to be effective, though there were 13 non-responders in the clofibrate group, compared with 8 in the gemfibrozil group. The mean reduction in serum cholesterol induced by clofibrate was 23% and by gemfibrozil 19%. The corresponding falls in serum triglycerides were 36% and 43%. There were no serious side effects in either group. Analysed in this way, the relative efficiencies of gemfibrozil and clofibrate seem to be indistinguishable. Further studies are being directed towards evaluation of the individual responses to both treatments.

The lipoprotein lowering effect of gemfibrozil, 400 mg twice daily, was studied for 24 weeks in 26 subjects with primary hyperlipoproteinaemia (type IIa, 5; IIb, 3; III, 3; and IV, 15). Maximum effects were noted after four weeks on very low density lipoproteins (VLDL) and after 12 weeks on low density lipoproteins (LDL), these effects remaining throughout the study. Gemfibrozil decreased VLDL triglycerides (TG) in all types of hyperlipoproteinaemia according to the equation: deltaVLDL TG (mmol/l) = -0.80 X initial VLDL TG concentration + 0.68 The drug affected the low density lipoprotein (LDL) cholesterol= -0.45 X initial LDL cholesterol + 61 This means that LDL cholesterol on average decreased if the initial LDL concentration was above 135 mg/100 ml and increased below that concentration. LDL TG and high density lipoprotein (HDL) TG concentrations also decreased significantly. A slight increase in HDL cholesterol concentration occurred after administration of gemfibrozil. Two subjects had to stop treatment because of nausea and abdominal pain respectively, attributed to the drug. No biochemical side effects were noted.