Effects of pioglitazone on macrovascular events in patients with type 2 diabetes mellitus at high risk of stroke: the PROFIT-J study.
OBJECTIVE
The present study evaluated the effects of pioglitazone treatment on the incidence of primary cardiovascular events in Japanese subjects with type 2 diabetes mellitus at high risk of stroke.


METHODS
A prospective, multicenter, randomized, open label, comparative study was conducted among diabetic patients recruited from 50 medical institutions nationwide. A total of 522 patients with hypertension and/or dyslipidemia who had one or more silent cerebral infarcts, advanced carotid atherosclerosis or microalbuminuria at baseline were randomly treated with (n=254) or without pioglitazone (n=268) and observed for a medium of 672 days. The hypertension and dyslipidemia were concurrently treated according to the respective treatment guidelines. The primary outcome was the time to the first occurrence of a composite of all-cause death, nonfatal cerebral infarction and nonfatal myocardial infarction.


RESULTS
Treatment with pioglitazone resulted in significant reductions in the levels of HbA1c, diastolic blood pressure and LDL-cholesterol and a significant increase in the levels of HDL-cholesterol. The pioglitazone non-users exhibited a significant reduction in the LDL-cholesterol levels alone. Primary events were registered during the study period in nine patients in the pioglitazone group and 10 patients in the non-pioglitazone group. The difference in the cumulative incidence of the primary outcome was not significant between the two groups(1.8% per year).


CONCLUSIONS
Pioglitazone therapy produces immediate and effective improvements in glycemic control, diastolic blood pressure and lipid profiles. While this study was too underpowered to determine the effects of pioglitazone on the incidence of cardiovascular events, the results indicated that two years of pioglitazone treatment did not produce any statistically significant reductions in the rate of primary cardiovascular events.
Department of Medicine, Diabetology and Endocrinology, Juntendo Tokyo Koto Geriatric Medical Center, Juntendo University School of Medicine.
Hidenori
H
Yoshii
Tomio
T
Onuma
Tsutomu
T
Yamazaki
Hirotaka
H
Watada
Munehide
M
Matsuhisa
Masayasu
M
Matsumoto
Kazuo
K
Kitagawa
Masafumi
M
Kitakaze
Yoshimitsu
Y
Yamasaki
Ryuzo
R
Kawamori
D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure; D048909:Diabetes Complications / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D050171:Dyslipidemias / Q000150:complications / Q000188:drug therapy; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D011446:Prospective Studies; D020521:Stroke / Q000150:complications* / Q000188:drug therapy; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome
D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000077205:Pioglitazone; D045162:Thiazolidinediones; C517652:hemoglobin A1c protein, human