Rehabilitation of pioglitazone

This house believes that sulphonylureas should not be used routinely as second-line treatments for patients with type 2 diabetes

“…15 Further research has shown that there is no increased risk of bladder cancer with pioglitazone, as had been suggested. 15 Cardiovascular outcomes -don't forget incretin agents and SGLT2 inhibitors New regulations in the USA require a postmarketing cardiovascular outcomes trial for most new diabetes therapies. As a result, a steady stream of cardiovascular safety studies has continued to add to the list of newer antidiabetic agents that have not been associated with an increased risk of adverse cardiovascular outcomes.…”

“…Recent reconsideration of the PROactive trial (a randomised, placebo-controlled evaluation of pioglitazone in 5,283 patients at high cardiovascular risk) has enabled us to see beyond the limitations of the design of that trial. 14,15 Initial discussion of PROactive focused on the flawed primary endpoint of that trial; this was not affected significantly by pioglitazone but contained an outcome related to a procedure, which likely confounded the outcome. The principal secondary outcome (all-cause mortality, nonfatal MI or stroke) was reduced by pioglitazone (by 16% vs. placebo) and is highly relevant to the cardiovascular events suffered by diabetes patients.…”

“…Further analyses from PROactive have confirmed significant protection by pioglitazone from recurrent MI or stroke. 15 The efficacy of pioglitazone must be balanced against its tolerability: be cautious in prescribing pioglitazone where risk of fractures is of particular concern (women at risk of osteoporosis) and watch carefully for oedema -excess fluid can often be unloaded successfully by co-prescribing a diuretic (which also reduces the risk of the congestive heart failure that has been associated with pioglitazone). 15 Further research has shown that there is no increased risk of bladder cancer with pioglitazone, as had been suggested.…”

“…15 The efficacy of pioglitazone must be balanced against its tolerability: be cautious in prescribing pioglitazone where risk of fractures is of particular concern (women at risk of osteoporosis) and watch carefully for oedema -excess fluid can often be unloaded successfully by co-prescribing a diuretic (which also reduces the risk of the congestive heart failure that has been associated with pioglitazone). 15 Further research has shown that there is no increased risk of bladder cancer with pioglitazone, as had been suggested. 15 Cardiovascular outcomes -don't forget incretin agents and SGLT2 inhibitors New regulations in the USA require a postmarketing cardiovascular outcomes trial for most new diabetes therapies.…”

The EMPA-REG study: What has it told us? A diabetologist’s perspective

“…Of particular note, recurrent stroke (HR = 0.53, p = 0.008) and recurrent MI (HR = 0.72, p = 0.045), which were not reduced in EMPA-REG, both were significantly reduced in PROactive. Pioglitazone has been shown to exert no negative ionotropic effects on left ventricular function, to improve diastolic dysfunction, to reduce blood pressure (after load), and to improve endothelial dysfunction (Clarke et al, 2014; Eldor, DeFronzo, & Abdul-Ghani, 2013; Ryder & DeFronzo, 2015). The fluid retention observed with pioglitazone is related to the drug’s sodium retentive effect on the kidney.…”