Observational follow‐up of the PROactive study: a 6‐year update1. Issue 1 (19th August 2013)

• Record Type: Journal Article
• Authors: Erdmann, E.; Song, E.; Spanheimer, R.; van Troostenburg de Bruyn, A.‐R.; Perez, A.
• Is Part Of: Diabetes, obesity & metabolism. Volume 16:Issue 1(2014:Jan.)
• Page Start: 63
• Page End: 74
• Publication Date: 2013-08-19
• Subjects: Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.12180
• Languages: English
• ISSNs: 1462-8902

Abstract

<abstract abstract-type="main" id="dom12180-abs-0001"> <title>Abstract</title> <sec id="dom12180-sec-0001" sec-type="section"> <title>Aims</title> <p id="dom12180-para-0001">The PROactive study investigated pioglitazone for secondary prevention of macrovascular events in type 2 diabetes mellitus. Pioglitazone showed a 10% (non‐significant) relative risk (RR) reduction for the primary composite endpoint and a significant 16% reduction for the main secondary endpoint (death, myocardial infarction, stroke) after a mean 34.5 months. There was no difference in cumulative malignancy incidence, but an imbalance in bladder malignancies (pioglitazone 14, placebo 5). We present a pre‐specified 6‐year interim analysis of a 10‐year observational follow‐up.</p> </sec> <sec id="dom12180-sec-0002" sec-type="section"> <title>Methods</title> <p id="dom12180-para-0002">Any patient completing PROactive was eligible. No study treatments were provided. A Cox proportional hazard model compared non‐adjudicated macrovascular events (same endpoints as PROactive excluding acute coronary syndrome) based on original randomization. Malignancies were compared using conventional RR ratios.</p> </sec> <sec id="dom12180-sec-0003" sec-type="section"> <title>Results</title> <p id="dom12180-para-0003">Of 5238 randomized patients, 3599 (74%) entered the follow‐up. For the follow‐up (mean 5.8 years) or combined double‐blind and follow‐up periods (≤9.5 years, mean 8.7), there were no statistically significant differences in primary or main secondary endpoints. For the combined period, a similar percentage of patients had any diagnosed malignancy (RR = 1.05, 95% CI [0.89, 1.24]) or bladder malignancy (RR = 1.06, 95% CI [0.59, 1.89]) in the pioglitazone and placebo groups. There were fewer cases of bladder malignancy with pioglitazone (15 [0.6%] vs. 19 [0.7%] for placebo) for the combined period when events diagnosed in the first 365 days were excluded, and fewer cases for the follow‐up period alone (10 [0.5%] vs. 17 [1.0%] for placebo). Further analyses of pioglitazone use (including use during follow‐up) found no significant difference in bladder malignancies between any and no pioglitazone use for the combined period.</p> </sec> <sec id="dom12180-sec-0004" sec-type="section"> <title>Conclusions</title> <p id="dom12180-para-0004">These data suggest that improved macrovascular outcomes seen with pioglitazone subside without continued pioglitazone treatment. The double‐blind period bladder cancer imbalance did not persist in follow‐up.</p> </sec> </abstract>