Improving macrovascular outcomes in type 2 diabetes: Outcome studies in cardiovascular risk and metabolic control

Type 2 diabetes is accompanied by a host of potentially modifiable cardiovascular disease risk factors. Consequently, people with type 2 diabetes have a higher risk of macrovascular disease than the non-diabetic population, and a poor prognosis following an event. Several large-scale primary and secondary outcome studies have included large diabetes subgroups for post-hoc analysis, and a limited number of studies have focused specifically on type 2 diabetes.

This review provides an overview of macrovascular outcome studies in type 2 diabetes and discusses potential new targets for therapy based upon a MEDLINE literature search from January 1990 to April 2006.

Large cardiovascular outcome studies show that treating cardiovascular disease risk factors significantly reduces the risk of primary and secondary macrovascular events in patients with type 2 diabetes. The evidence for targeting hypertension (using renin-angiotensin system inhibitors), dyslipidemia (statins), and coagulation factors (aspirin) appears robust. However, the macrovascular benefits of improved glucose control remain to be proven definitively, although metformin may have advantages over other glucose-lowering agents. Nevertheless, these studies reveal that significant excess residual risk remains, highlighting the need for new therapies. It is also apparent that some agents (e.g. metformin, statins, renin-angiotensin system inhibitors) may also have pleiotropic mechanisms. Newer strategies are investigating other lipid targets (especially HDL cholesterol) or using agents, such as thiazolidinediones, that address multiple established and emerging risk factors. A recent study with pioglitazone suggests that macrovascular risk can be reduced in very high-risk patients with type 2 diabetes who are already receiving contemporary lipid, anti-hypertensive, and anti-platelet therapy.

The core therapeutic paradigm targeting glycemia, hypertension, dyslipidemia, and coagulation factors has failed to remove excess residual risk in patients with type 2 diabetes completely. Emerging data, and on-going trials, should provide better guidance on new therapeutic opportunities in this high-risk patient group.