Effects of Pioglitazone for Secondary Stroke Prevention in Patients with Impaired Glucose Tolerance and Newly Diagnosed Diabetes: The J-SPIRIT Study.
OBJECTIVE
Prediabetes is an independent risk factor for future stroke. However, no effective treatment has yet been established for the recurrence of stroke in patients with prediabetes. Here we investigated the effects of pioglitazone, a potent peroxisome proliferator-activated receptor-gamma agonist, for the reduction of recurrent stroke in patients with prediabetes.


METHODS
Participants were patients who had a symptomatic ischemic stroke or transient ischemic attack (TIA) without a history of type 2 diabetes mellitus and who were diagnosed to have IGT or newly diagnosed diabetes by a 75-g oral glucose tolerance test. These patients were randomized to either receive or not receive pioglitazone. The primary endpoint was a recurrence of ischemic stroke.


RESULTS
A total of 120 patients were enrolled in the study. Sixty-three patients received pioglitazone and 57 were enrolled in the control group that did not receive pioglitazone. The majority of patients (68.3%) were prescribed 15 mg of pioglitazone, while the remaining patients (31.7%) were treated with 30 mg of pioglitazone. Over a median follow-up period of 2.8 years, treatment with pioglitazone was found to be associated with a lower rate of the primary endpoint (recurrence of stroke) than that observed in the control group [event rate=4.8% pioglitazone vs 10.5% control, hazard ratio=0.62, 95% confidence interval 0.13-2.35, p=0.49]. However, differences were not statistically significant.


CONCLUSIONS
While this study was too underpowered to determine the effect of pioglitazone, the result failed to show beneficial effects in patients of ischemic stroke or TIA with impaired glucose tolerance and newly diagnosed diabetes.
Department of Neurology, Juntendo University School of Medicine.
Ryota
R
Tanaka
Kazuo
K
Yamashiro
Yasuyuki
Y
Okuma
Hideki
H
Shimura
Shinichiro
S
Nakamura
Yuji
Y
Ueno
Yasutaka
Y
Tanaka
Nobukazu
N
Miyamoto
Yuji
Y
Tomizawa
Toshiki
T
Nakahara
Yoshiaki
Y
Furukawa
Hirotaka
H
Watada
Ryuzo
R
Kawamori
Nobutaka
N
Hattori
Takao
T
Urabe
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D005260:Female; D018149:Glucose Intolerance / Q000150:complications / Q000175:diagnosis; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000819:agonists; D000077205:Pioglitazone; D011236:Prediabetic State / Q000150:complications / Q000175:diagnosis; D011446:Prospective Studies; D012008:Recurrence; D012307:Risk Factors; D055502:Secondary Prevention / Q000379:methods; D020521:Stroke / Q000473:pathology / Q000517:prevention & control*; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome
D047495:PPAR gamma; D045162:Thiazolidinediones; D000077205:Pioglitazone