T. Toyota et al., 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, CLIN DRUG I, 21(5), 2001, pp. 325-335
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 impa
ired glucose tolerance (IGT) or type 2 diabetes mellitus (DM) associated wi
th hypertriglyceridaemia (fasting serum triglycerides greater than or equal
to 150 mg/dl) untreated with insulin, 81 of whom were evaluated for drug e
Design: Patients enrolled were randomised to receive either cilostazol (gro
up C) 200 mg/day or placebo (group P) [two tablets twice a day after breakf
ast 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-wee
k administration period. Lipid parameters, uric acid and glycaemic control
were measured at baseline (weeks -4, 0) and 4, 8 and 12 weeks after treatme
nt. For each primary study variable, final assessment was based on the chan
ge 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 lipo
protein cholesterol (HDL-C) increased significantly (p <less than> 0.05) fr
om 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 ov
er 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 signific
antly (p < 0.001) from 38 +/- 7 to 44 +/- IO mg/dl and the difference betwe
en groups P and C was also significant (p < 0.01). In group C, apolipoprote
in 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 sign
ificantly (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 gl
ucose level and HbA(1c) level) was not affected by either treatment. Abnorm
al 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 differen
ce 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 incre
ased bleeding tendencies or frank haemorrhage were noted in any patient.
Conclusions: In IGT or type 2 DM patients with hypertriglyceridaemia, cilos
tazol 200mg effectively lowers TG and uric acid levels, and shows a potenti
ally important effect in increasing HDL-C levels without significantly affe
cting glycaemic control. These results indicate that the clinical effect of
cilostazol on lipid and uric acid metabolism is a beneficial effect that p
rotects against atherosclerotic disease.