Effect of cilostazol on lipid, uric acid and glucose metabolism in patients with impaired glucose tolerance or type 2 diabetes mellitus - A double-blind, placebo-controlled study

Objective: The aim of this study was to assess the effects of cilostazol on the metabolic profiles of serum lipids, uric acid and glycaemic control. Patients: This was a comparative study in a total of 112 patients with impaired glucose tolerance (IGT) or type 2 diabetes mellitus (DM) associated with hypertriglyceridaemia (fasting serum triglycerides greater than or equal to 150 mg/dl) untreated with insulin, 81 of whom were evaluated for drug efficacy. Design: Patients enrolled were randomised to receive either cilostazol (group C) 200 mg/day or placebo (group P) [two tablets twice a day after breakfast and dinner] for 12 weeks according to a double-blind method. The study consisted of a 4-week run-in period (week-4 to week 0) followed by a 12-week administration period. Lipid parameters, uric acid and glycaemic control were measured at baseline (weeks -4, 0) and 4, 8 and 12 weeks after treatment. For each primary study variable, final assessment was based on the change observed after 12 weeks of administration relative to the baseline value obtained at week 0. Results: In group C, triglycerides (TG) decreased significantly (p < 0.05) from 238 +/- 85 to 193 +/- 105 mg/dl, but increased in group P There was a significant (p < 0.05) difference between the two groups. High density lipoprotein cholesterol (HDL-C) increased significantly (p <less than> 0.05) from 39 +/- 10 to 41 +/- 11 mg/dl in group P. HDL-C in group C also increased but not significantly. When the results of one patient, whose HDL-C was over 100 mg/dl, were excluded, HDL-C in group C changed similarly to that in the subgroup (HDL-C level at baseline < 50 mg/dl), which increased significantly (p < 0.001) from 38 +/- 7 to 44 +/- IO mg/dl and the difference between groups P and C was also significant (p < 0.01). In group C, apolipoprotein B (apo B) decreased significantly (p < 0.01) from 155 <plus/minus> 24 to 140 +/- 28 mg/dl and apolipoprotein E (apo E) decreased significantly (p < 0.01) from 7.8 +/- 1.9 to 6.7 +/- 2.0 mg/dl. Uric acid also decreased significantly (p < 0.01) from 5.8 +/- 1.5 to 5.3 +/- 1.4 mg/dl in group C, but did not decrease significantly in group P, indicating a significant (p < 0.05) difference between the two groups. Glycaemic control (fasting plasma glucose level and HbA(1c) level) was not affected by either treatment. Abnormal laboratory findings were seen in 25.5% ( 14/55) of the patients in group P and in 14.3% (8/56) of those in group C, showing no significant difference between the two groups. Drug-related adverse events were observed in 7.3% (4/55) of the patients in group P and in 35.7% (20/56) of those in group C, indicating a significant (p < 0.001) difference between the two groups. Headache was the most frequent complaint (15 patients in group C). No increased bleeding tendencies or frank haemorrhage were noted in any patient. Conclusions: In IGT or type 2 DM patients with hypertriglyceridaemia, cilostazol 200mg effectively lowers TG and uric acid levels, and shows a potentially important effect in increasing HDL-C levels without significantly affecting glycaemic control. These results indicate that the clinical effect of cilostazol on lipid and uric acid metabolism is a beneficial effect that protects against atherosclerotic disease.