Drug-induced changes in risk/biomarkers and their relationship with renal and cardiovascular long-term outcome in patients with diabetes.

Background: Optimal renal and cardiovascular risk management in diabetic patients includes optimal maintenance of blood pressure and control of glucose and lipids. Although the optimal control of these risk factors or "risk/biomarkers" has proven to be effective, it often is difficult to achieve. Consequently, the risk for renal and cardiovascular complications remains devastatingly high. Many risk/biomarkers have been discovered that accurately predict long-term renal and cardiovascular outcome. However, the aim of measuring risk/biomarkers may not be only to determine an individual's risk, but also to use the risk/biomarker level to guide therapy and thereby improve long-term clinical outcome.

Content: This review describes the effects of various drugs on novel risk/biomarkers and the relationship between (drug induced) short-term changes in risk/biomarkers and long-term renal and cardiovascular outcome in patients with diabetes.

Summary: In post hoc analyses of large trials, the short-term reductions in albuminuria, transforming growth factor-β, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) induced by inhibitors of the renin-angiotensin-aldosterone system were associated with a decreased likelihood of long-term adverse renal and cardiovascular outcomes. However, the few studies that systematically investigated the utility of prospectively targeting novel risk/biomarkers such as hemoglobin or NT-proBNP failed to demonstrate long-term cardiovascular protection. The latter examples suggest that although a risk/biomarker may have superior prognostic ability, therapeutically changing such a risk/biomarker does not necessarily improve long-term outcome. Thus, to establish the clinical utility of other novel risk/biomarkers, clinical trials must be performed to prospectively examine the effects of therapeutically-induced changes in single or multiple risk/biomarkers on long-term risk management of patients with diabetes.