The role of renin inhibition in treating the hypertensive patient with diabetes: a summary of preclinical and clinical evidence

Comorbid hypertension and diabetes is common and associated with substantially greater cardiovascular and renal risk relative to hypertension alone. Tissue renin-angiotensin system (RAS) overactivity is a hallmark of diabetes and contributes to target organ damage. Treatment guidelines recommend angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for reducing cardiorenal risk in patients with hypertension plus diabetes. However, these agents only partially prevent cardiovascular and renal morbidity/mortality. Further attempts to improve clinical outcomes have focused on the use of an ACE inhibitor plus an ARB, but this combination has not demonstrated a favorable risk-benefit profile. Direct renin inhibitors provide a more comprehensive blockade of the RAS compared with ACE inhibitors or ARBs, and may be of particular benefit in counteracting tissue RAS overactivity. In this article, the role of the RAS in diabetic hypertension and the preclinical and clinical effects of direct renin inhibitor therapy on target organs are reviewed.