SOURCE: Inzucchi SE, Viscoli CM, Young LH, et al. Pioglitazone prevents diabetes in patients with insulin resistance and cerebrovascular disease. Diabetes Care 2016;39:1684-1692.

The Insulin Resistance After Stroke (IRIS) trial randomized patients with recent ischemia stroke or transient ischemic attack to pioglitazone (PIO) or placebo for approximately five years. The rationale for selecting PIO was that these patients were all prediabetic, as defined by the homeostatic model assessment-insulin resistance score, further supported by their mean A1c (5.8). To be clear: diabetics were excluded from the trial; only prediabetics were included.

The primary endpoint of the IRIS trial indicated a significant 24% reduction in new stroke with PIO. This follow-up report detailed the ability of PIO to prevent development of diabetes in this population of prediabetics.

Over a five-year interval, 7.7% of placebo recipients progressed from prediabetes to diabetes, compared with 3.8% of the PIO group (hazard ratio = 0.48). Predictably, those prediabetics with the greatest degree of fasting blood glucose perturbation and highest baseline A1c showed the greatest degree of benefit.

PIO reduces vascular events in insulin-resistant stroke victims, as well as reduces risk of progression from prediabetes to diabetes by > 50%.