What is the comparison between Angiotensin-Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs) in patients with diabetes?

From the Guidelines

In patients with diabetes, both ACE inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs) are effective first-line treatments for hypertension, but the most recent evidence suggests that either class can be used, with the choice between them often coming down to tolerability and patient-specific factors. The most recent study, published in 2024 1, found that ACE inhibitors and ARBs have similar effects on renal outcomes in patients with diabetes. Common ACEIs include lisinopril (10-40 mg daily), ramipril (2.5-20 mg daily), and enalapril (5-40 mg daily). ARBs such as losartan (25-100 mg daily), valsartan (80-320 mg daily), or irbesartan (150-300 mg daily) are excellent alternatives, particularly when patients experience the dry cough side effect from ACEIs.

Key Points

• Both ACEIs and ARBs provide similar cardiovascular and renal protection by targeting the renin-angiotensin-aldosterone system, though they do so through different mechanisms.
• ACEIs block the conversion of angiotensin I to angiotensin II, while ARBs block angiotensin II receptors directly.
• Both reduce blood pressure, decrease albuminuria, slow diabetic nephropathy progression, and provide cardiovascular protection.
• In patients with diabetic nephropathy with proteinuria, either class is strongly recommended.
• If maximum doses of either medication don't adequately control blood pressure, adding a thiazide diuretic, calcium channel blocker, or switching to the other class may be necessary rather than combining ACEIs and ARBs, as dual therapy increases adverse effects without significant benefit, as noted in a 2021 study 1.

Considerations

• The choice between ACEIs and ARBs often comes down to tolerability, with ARBs having fewer side effects overall.
• Patients with diabetes and hypertension should receive RAS inhibitors, which should be titrated to the maximal tolerated dose, with close monitoring of serum potassium and serum creatinine levels, as recommended in a 2021 guideline 1.
• Combination therapy with ACEIs and ARBs is harmful and should be avoided in patients with diabetes and CKD, as it increases the risk of hyperkalemia and AKI, as noted in a 2022 consensus report 1.

From the FDA Drug Label

In trials in which valsartan was compared to an ACE inhibitor with or without placebo, the incidence of dry cough was significantly greater in the ACE-inhibitor group (7.9%) than in the groups who received valsartan (2.6%) or placebo (1.5%). Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements and/or potassium-containing salt substitutes, which should be used cautiously, if at all, with enalapril maleate

The comparison between Angiotensin-Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs) in patients with diabetes shows that:

• ACE inhibitors have a higher incidence of dry cough (7.9%) compared to ARBs (2.6%) and placebo (1.5%) 2.
• Diabetes mellitus is a risk factor for the development of hyperkalemia when using ACE inhibitors like enalapril maleate 3. It is essential to exercise caution when using ACE inhibitors or ARBs in patients with diabetes, especially when combined with other medications that may increase the risk of hyperkalemia.

From the Research

Comparison of ACE Inhibitors and ARBs in Patients with Diabetes

• Both ACE inhibitors and ARBs can slow the progression of diabetic nephropathy, as they can reduce proteinuria and decrease the risk of end-stage renal disease (ESRD) 4, 5, 6.
• The optimal dosage of ACE inhibitors or ARBs required to slow the progression of renal disease or impair the development of cardiovascular risk is not known, but higher doses may be more effective in reducing proteinuria 6.
• ACE inhibitors have been reported to improve kidney, heart, and to a lesser extent, eye and peripheral nerve function of patients with diabetes mellitus, due to their inhibition of both haemodynamic and tissular effects of angiotensin II 7.
• ACE inhibitor therapy reduces both microvascular and macrovascular complications in diabetes, improves insulin sensitivity and glucose metabolism, and reduces the development of type 2 diabetes in persons with essential hypertension 8.
• Combination therapy of ACE inhibitors and ARBs may be beneficial in decreasing the progression of diabetic nephropathy, but its effect in slowing progression is unknown, and the potential for hyperkalemia may limit its utility in this population 4.

Key Differences and Similarities

• Both ACE inhibitors and ARBs are powerful medications for the prevention of progression of diabetic renal disease, but their effects on cardiovascular disease and renal disease may differ 5, 8.
• ACE inhibitors and ARBs have unique capabilities as antihypertensive agents, and their use is recommended in patients with diabetes and hypertension, cardiovascular disease, or those who are at risk of cardiovascular disease 5, 7.
• The use of ACE inhibitors or ARBs is also recommended in the management of diabetic kidney disease in elderly patients, with monitoring of renal function and potassium levels 5.

Clinical Implications

• ACE inhibitors and ARBs should be considered as first-line therapeutic agents for treating hypertension in patients with diabetes, due to their ability to reduce microvascular and macrovascular complications 8.
• The dose-response relationship for diabetic renal disease should be determined to accrue the optimum benefit from ACE inhibitors and ARBs, and the best strategy, such as supramaximal doses or combining them, is still a matter of debate 6.
• Professional societies recommend that elderly patients with diabetes and hypertension be treated with an ACE inhibitor or ARB, with monitoring of renal function and potassium levels 5.