Pioglitazone shows mixed results for adverse effects in type 2 diabetes and prediabetes

A new review of studies on the blood-sugar lowering drug pioglitazone has found mixed results when it comes to risks associated with its use in people with type 2 diabetes, prediabetes and insulin resistance.
Pioglitazone, sold under the trade name Actos, shows some success in reducing major adverse cardiovascular events, such as non-fatal myocardial infarctio, non-fatal stroke and cardiovascular death (MACE), but increases risks of heart failure.
The drug has also been found to carry higher risks of bone fracture and oedema (water retention), as well as causing weight gain.
A total of nine trials, conducted from 1966 to 2016 and involving over 120,100 participants, were scrutinised to evaluate the prevalence of adverse cardiovascular outcomes and other side effects.
These trials included participants with insulin resistance, prediabetes or type 2 diabetes, and some of them looked at the effect of pioglitazone in slowing down the development of diabetes among those with insulin resistance or prediabetes.
All of the studies had a mean follow-up of at least one year for complications with pioglitazone in participants, some of whom already had a history of cardiovascular disease (stroke or heart attack).
Statistically, taking pioglitazone conferred a 23 per cent risk reduction of serious cardiovascular outcomes, like MACE, among people with insulin resistance or prediabetes.
The reduction in MACE odds was less obvious, albeit still beneficial, in participants with type 2 diabetes, with a 17 per cent risk reduction. Pioglitazone also made none to very little difference to risks of myocardial infarction and stroke in people with type 2 diabetes. In addition to that, pioglitazone appears to increase risks of heart failure.
Apart from cardiovascular outcomes, previous studies suggested that there might be a link between pioglitazone use and bladder cancer, but no significant effect on bladder cancer risks has been observed in the meta-analysis.
As for the rate of progression of type 2 diabetes, participants with insulin resistance and prediabetes taking pioglitazone showed a slower development to diabetes in two of the trials analysed.
Overall, pioglitazone may offer some cardiovascular risk reduction benefits, but it can also notably increase other risks, such as heart failure, oedema, and weight gain.