Effects of Pioglitazone on Macrovascular Events in Patients with Type 2 Diabetes Mellitus at High Risk of Stroke: The PROFIT-J Study
Open Access
- 1 January 2014
- journal article
- research article
- Published by Japan Atherosclerosis Society in Journal of Atherosclerosis and Thrombosis
- Vol. 21 (6), 563-573
- https://doi.org/10.5551/jat.21626
Abstract
Aim: 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.Keywords
This publication has 28 references indexed in Scilit:
- Nuclear receptor transrepression pathways that regulate inflammation in macrophages and T cellsNature Reviews Immunology, 2010
- The effect of intensive glucose control on all-cause and cardiovascular mortality, myocardial infarction and stroke in persons with type 2 diabetes mellitus: a systematic review and meta-analysisDiabetes and Vascular Disease Research, 2009
- Relationship Between CarotidIntima-Media Thickness and Silent Cerebral Infarction in Japanese Subjects With Type 2 DiabetesDiabetes Care, 2009
- 10-Year Follow-up of Intensive Glucose Control in Type 2 DiabetesThe New England Journal of Medicine, 2008
- Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular CausesThe New England Journal of Medicine, 2007
- Incidence and Risk Factors for Stroke in Type 2 Diabetic PatientsStroke, 2007
- Intensive Diabetes Treatment and Cardiovascular Disease in Patients with Type 1 DiabetesThe New England Journal of Medicine, 2005
- Peroxisome proliferator–activated receptor γ ligands inhibit development of atherosclerosis in LDL receptor–deficient miceJCI Insight, 2000
- The Causes and Risk of Stroke in Patients with Asymptomatic Internal-Carotid-Artery StenosisThe New England Journal of Medicine, 2000
- Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)The Lancet, 1998