The rate of progression was 58% lower (95% CI, 48 66) with intensive counseling and 31% (95% CI, 17 43) lower with metfor- min compared with standard lifestyle counsel- ing. Metformin is well tolerated and inexpensive. Other drugs that have been shown to reduce progression to diabetes include pioglitazone,245 These are not as well tolerated as metformin. Liraglutide is delivered by injection. 8. Approximately 30% of patients with ischemic stroke have prediabetes as defined by HbA1c and other measures of glucose metabolism.255 Most of these patients will have insulin resistance as a contributing cause, but insulin resistance can occur before prediabetes develops. Thus, 50% of patients without diabetes with ischemic stroke have insulin resistance.269,270 Both condi- tions have been associated with increased risk for first ischemic stroke,252,253,271 275 but no research has been designed to test their effect on risk for recurrent vascular events. One large clinical trial has examined the effect of a specific interven- tion for patients with ischemic stroke and insu- lin resistance. The IRIS trial (Insulin Resistance Intervention After Stroke) examined the effect of the insulin-sensitizing agent pioglitazone compared with placebo among patients with- out diabetes who had a recent ischemic stroke and insulin resistance. Patients with heart failure were excluded. After a mean of 3.8 years, pio- glitazone reduced the risk of recurrent stroke or 11.8% among placebo recipients to 9.0% among pioglitazone recipients. Active treatment, however, was associated with weight gain and increased bone fracture risk. These adverse events have restrained clinical use of pioglitazone. Knowledge Gaps and Future Research Having T2D is one of the most prevalent risk factors for future stroke after an initial acute ischemic stroke or TIA. 