Insulin resistance is a major intermediate link between disordered glucose metabolism and macrovascular complications. The glitazones (pioglitazone, rosiglitazone) impact directly and selectively on the key problem of insulin resistance. In the meantime, much evidence has accumulated for a vessel-protective effect of the glitazone class of substances. Currently, major endpoint studies are investigating the extent to which, and under what conditions, a glitazone actually does influence the cardiovascular morbidity and mortality. The first results from the PROactive study--the design of which, together with the data at study begin have already been published--are expected to become available by the end of 2005.