Patients with diabetes have a two to four-fold increased risk of a cardiovascular event compared with non-diabetics. Until now there has only been indirect evidence suggesting that pioglitazone could reduce cardiovascular-related deaths and illness in diabetics.
John Dormandy (St George's Hospital, London, UK) and colleagues recruited 5238 patients with type 2 diabetes who had evidence of macrovascular disease from centres in 19 European countries. Participants were randomly assigned either pioglitazone (2605) or placebo (2633) in addition to their existing medication(s) for diabetes and cardiovascular disease. Patients were followed-up for an average of 34.5 months. The investigators found that for a combined endpoint of death, heart attack, stroke, acute coronary syndrome, and cardiac or leg interventions the treatment group had 803 events while the placebo group had 900 events. There were fewer adverse events in the treatment group, although there was an increase in reported heart failure, however, the number of deaths from heart failure were similar in each group. The researchers also found that patients receiving pioglitazone did not need to start taking insulin as soon as those assigned the placebo. The results indicate that giving 1000 patients pioglitazone would avoid 21 first heart attacks, strokes, or deaths over 3 years.
Professor Dormandy states: "...in patients with type 2 diabetes who are at high cardiovascular risk, pioglitazone improves cardiovascular outcome, and reduces the need to add insulin to glucose lowering-regimens compared with placebo...We believe our results are generalisable to all patients with type 2 diabetes."
In an accompanying comment Hannele Yki-Jarvinen (University of Helsinki, Finland) states: "Overall, PROactive is an important study that leaves us with some good news, some bad news, and some unknowns. The clinician, of course wants to know who should be treated with pioglitazone. Unfortunately, the study does not provide such answers. It showed that pioglitazone is beneficial in patients with type 2 diabetes and pre-existing macrovascular disease who do not develop heart failure."
Contact: Professor Dormandy via Alex Weaver T) 07834 254878 a.weaver@ncrl.co.uk
Professor Hannele Yki-Jarvinen, Department of Medicine, Division of Diabetes, University of Helsinki, PO Box 340, Haartmaninkatu 4, 00290 Helsinki, Finland
T) 00 358 9 471 72350 ykijarvi@mappi.helsinki.fi
Journal
The Lancet