Charbonnel et al.’s analysis of the PROactive trial demonstrated that pioglitazone plus insulin regimen yielded sustained improvements in glycemic control and reduced insulin doses, but it increased edema, hypoglycemia, and HF rates, with a non-significant 15% reduction in risk in the major secondary endpoint (i.e., a composite of nonfatal MI, stroke, and death) [30]. This evidence concerns the gene INS and Stroke.