Combination of ACE Inhibitor and ARB is Not Recommended for Patients with Diabetes and Hypertension
The combination of an ACE inhibitor and an ARB is contraindicated in patients with diabetes and hypertension due to lack of additional benefit and increased risk of adverse events including hyperkalemia, hypotension, and acute kidney injury. 1, 2, 3
Evidence Against Dual RAAS Blockade
The American Diabetes Association's 2025 Standards of Care explicitly states that "the combination of an ACE inhibitor and ARB and the combination of an ACE inhibitor or ARB and a direct renin inhibitor is contraindicated given the lack of added ASCVD benefit and increased rate of adverse events" 1. This recommendation is based on multiple clinical trials showing:
- Increased risk of hyperkalemia
- Higher rates of syncope
- Greater incidence of acute kidney injury
- No additional cardiovascular or renal benefit
The FDA drug labels for both ACE inhibitors and ARBs specifically warn against dual blockade of the renin-angiotensin system, noting that it's "associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy" 2, 3.
Appropriate RAAS Blockade in Diabetes
Instead of dual therapy, the following approach is recommended:
For patients with diabetes, hypertension, and albuminuria: Use a single RAAS blocker (either ACE inhibitor or ARB) as first-line therapy and titrate to the highest approved dose that is tolerated 1.
For patients with normal albumin excretion: Either an ACE inhibitor, ARB, thiazide-like diuretic, or dihydropyridine calcium channel blocker can be used as first-line therapy 1.
For blood pressure not at target: Add complementary agents from different classes rather than combining ACE inhibitors and ARBs 4:
- Dihydropyridine calcium channel blockers
- Thiazide-like diuretics
- Mineralocorticoid receptor antagonists (if appropriate)
Monitoring Recommendations
When using a single RAAS blocker (either ACE inhibitor or ARB):
- Monitor serum creatinine and potassium within 2-4 weeks after initiation or dose change 1
- Continue therapy unless serum creatinine rises by more than 30% 1
- Perform annual monitoring of serum creatinine/eGFR and potassium 1
- Manage hyperkalemia when possible rather than immediately discontinuing the medication 1
Special Considerations
Pregnancy risk: ACE inhibitors and ARBs should be avoided in sexually active individuals of childbearing potential who are not using reliable contraception and are contraindicated in pregnancy 1.
Resistant hypertension: For patients not meeting blood pressure targets on three classes of antihypertensive medications (including a diuretic), consider adding a mineralocorticoid receptor antagonist rather than combining ACE inhibitors and ARBs 1.
While some older research suggested potential benefits of dual RAAS blockade for reducing proteinuria 5, subsequent larger trials have consistently demonstrated that the risks outweigh any potential benefits, leading to the current strong recommendations against this practice in clinical guidelines 4.