Combination Therapy With Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Antagonists in the Treatment of Patients With Type 2 Diabetes Mellitus

Abstract

Aggressive therapy for patients with type 2 diabetes mellitus and renal disease is warranted given the natural history of this disease. Although antagonizing the renin-angiotensin system is clearly important, how this is accomplished is of considerable controversy. On the one hand, recent clinical trials of patients with type 2 diabetes mellitus with renal disease demonstrate unequivocally the renal protective effect of angiotensin receptor blockers (ARBs). Although the results of the recently published LIFE trial are encouraging, inconsistencies have been observed with ARBs in reducing cardiovascular end points. On the other hand, angiotensin-converting enzyme inhibitors have a dramatic effect in reducing cardiovascular events but have not been shown convincingly to reduce progression of renal disease in patients with type 2 diabetes mellitus. These studies leave us in a quandary as to the optimal initial treatment regimen for patients with type 2 diabetes mellitus and renal disease despite the recent recommendations from the American Diabetes Association (Alexandria, Va). Given the fact that many of these individuals will require administration of multiple antihypertensive agents, perhaps the initial treatment with a combination of an ARB and angiotensin-converting enzyme inhibitor affords optimal cardiovascular and renal protection for patients with type 2 diabetes mellitus and renal disease. Future clinical trials should be designed to address this issue.

ACE Inhibitor or Angiotensin II Receptor Antagonist Attenuates Diabetic Neuropathy in Streptozotocin-Induced Diabetic Rats

“…Unlike some reports suggesting synergy for treatment of diabetic nephropathy or hypertension when ACE inhibitors were combined with angiotensin II receptor antagonists, we found no evidence of synergy for preventing/reversing vascular and neural dysfunction related to diabetic neuropathy when we combined enalapril and L-158809 (37)(38)(39). Third, we found that treatment of diabetic rats with enalapril or L-158809 prevented/reversed superoxide formation by the aorta.…”

Masterclass series in peripheral arterial disease

“…48 43 blockade of the renin-angiotensin-aldosterone system, and inhibiting the breakdown of vasoprotective factors such as bradykinin) there is no scientific clinical trial evidence that combination therapy is superior to single drug therapy with an ACE inhibitor or ARB. 52 Summary recommendations (Table 3) Patients with hypertension and PAD should be treated with a comprehensive program of risk factor modification. If no contraindications exist, patients should receive a statin and an antiplatelet agent to lower overall cardiovascular risk.…”

Diabetic Glomerulopathy

“…There are studies suggesting that dual blockade of renin-angiotensin system using a combination of ACE inhibitor and an ARB in patients with nephropathy is superior to the use of either drug alone. (Ayodele OE 2004, Mogensen CE 2000, Rosner MH 2003 (Bakris GL 1990 and Their antiproteinuric effect may be due to reduction in intraglomerular pressure, reduction in glomerular hypertrophy, and improved glomerular size. The dihydropyridine calcium channel blockers have a variable effect on protein excretion ranging from increased protein excretion to no effect to a fall in protein excretion in various studies.…”