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Ten‐year observational follow‐up of PROactive : a randomized cardiovascular outcomes trial evaluating pioglitazone in type 2 diabetes
Author(s) -
Erdmann E.,
Harding S.,
Lam H.,
Perez A.
Publication year - 2016
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12608
Subject(s) - pioglitazone , medicine , placebo , hazard ratio , type 2 diabetes , stroke (engine) , myocardial infarction , prostate cancer , randomized controlled trial , diabetes mellitus , cancer , urology , confidence interval , endocrinology , pathology , mechanical engineering , alternative medicine , engineering
Aims To conduct a 10‐year, observational follow‐up of patients completing PROactive to investigate whether trends of cardiovascular benefit with pioglitazone and imbalances in specific malignancies persisted over time. Methods Macrovascular endpoints and malignancies were compared based on original randomization to pioglitazone or placebo and ‘any’ versus ‘no’ pioglitazone use for bladder and prostate cancer. Results Of 4873 patients completing the PROactive trial, 74% entered the follow‐up. During follow‐up (mean 7.8 years), there were no statistically significant differences in the primary [all‐cause mortality, myocardial infarction ( MI ), cardiac intervention, stroke, major leg amputation, leg revascularization] or main secondary (death, MI , stroke) endpoints for subjects originally randomized to pioglitazone and placebo, except for leg amputations during follow‐up [4.1% pioglitazone, 5.6% placebo; hazard ratio 0.74, 95% confidence interval ( CI ) 0.55–0.99; p = 0.046]. During follow‐up, the incidence of total malignancies was similar between groups; bladder cancer was reported in 0.8% of patients (n = 14) in the pioglitazone versus 1.2% (n = 21) in the placebo group [relative risk ( RR ) 0.65, 95% CI 0.33–1.28], and prostate cancer was reported in 44 men (3.7%) in the pioglitazone versus 29 men (2.5%) in the placebo group ( RR 1.47, 95% CI 0.93–2.34). Conclusions The trends of macrovascular benefits of pioglitazone compared with placebo during PROactive did not persist in the absence of continued pioglitazone during this 10‐year follow‐up. Trends of decreased bladder cancer and increased prostate cancer were observed in the pioglitazone group during follow‐up; however, these imbalances should be interpreted with caution because of the limitations of the observational study design.