Should a diabetic patient without hypertension be on an Angiotensin-Converting Enzyme (ACE) inhibitor or Angiotensin Receptor Blocker (ARB)?

ACE Inhibitors and ARBs in Diabetic Patients Without Hypertension

Do not prescribe ACE inhibitors or ARBs to diabetic patients without hypertension unless they have albuminuria (UACR ≥30 mg/g). 1

Evidence-Based Decision Algorithm

The decision to use ACE inhibitors or ARBs in diabetic patients without hypertension depends entirely on kidney status, not cardiovascular risk alone:

Step 1: Measure Kidney Function Annually

• Obtain spot urinary albumin-to-creatinine ratio (UACR) and estimated GFR (eGFR) in all diabetic patients at least annually. 1
• For type 1 diabetes, begin screening after 5 years of disease duration. 2
• For type 2 diabetes, begin screening at diagnosis. 2

Step 2: Stratify by Albuminuria Status

Normal Albuminuria (UACR <30 mg/g):

• Do not prescribe ACE inhibitors or ARBs, even for "cardioprotection." 1
• The 2014 American Diabetes Association guidelines explicitly state: "An ACE inhibitor or ARB for the primary prevention of diabetic kidney disease is not recommended in diabetic patients with normal blood pressure and albumin excretion <30 mg/24 h." 2
• Clinical trial evidence shows no benefit and potential harm: one major trial in type 2 diabetic patients with normal urinary albumin excretion found that ARB therapy actually increased cardiovascular events despite reducing albuminuria development. 1

Moderate Albuminuria (UACR 30-299 mg/g):

• Prescribe either an ACE inhibitor or ARB regardless of blood pressure status. 2, 1
• Both drug classes delay progression to macroalbuminuria in type 2 diabetes with microalbuminuria. 2
• ACE inhibitors have been shown to delay nephropathy progression in type 1 diabetes with any degree of albuminuria. 2
• Titrate to maximum tolerated dose for optimal kidney protection. 1

Severe Albuminuria (UACR ≥300 mg/g):

• Strongly prescribe either an ACE inhibitor or ARB as first-line therapy regardless of blood pressure. 2, 1
• ARBs have been shown to delay nephropathy progression in type 2 diabetes with macroalbuminuria and renal insufficiency. 2
• This represents established diabetic kidney disease requiring renin-angiotensin system blockade. 1

Critical Monitoring Requirements

• Check serum creatinine/eGFR and serum potassium within 2-4 weeks of initiating therapy or changing doses. 1
• Continue monitoring at least annually thereafter. 1
• Tolerate acute eGFR decreases ≤30% after initiation, but investigate if decline exceeds 30%. 3

Common Pitfalls to Avoid

Never prescribe for "cardioprotection" alone:

• The 2009 ACC/AHA heart failure guidelines note that while ACE inhibitors reduced heart failure onset in diabetic patients, this benefit was primarily seen in those with hypertension or other cardiovascular complications. 2
• In diabetic patients without kidney disease or hypertension, ACE inhibitors and ARBs are not superior to other antihypertensive classes for cardiovascular outcomes. 2, 1

Never combine ACE inhibitors and ARBs:

• Multiple clinical trials demonstrate no additional cardiovascular or kidney benefits from combination therapy. 1, 4
• Combination therapy significantly increases adverse events including hyperkalemia and acute kidney injury. 1, 4

Do not underdose:

• Clinical trials demonstrating efficacy used maximum tolerated doses. 4
• Titrate to the highest approved dose for blood pressure treatment. 4

Monitor for hyperkalemia:

• Risk increases with reduced eGFR (<60 mL/min/1.73 m²), concomitant NSAIDs, potassium-sparing diuretics, or mineralocorticoid receptor antagonists. 1, 4
• Check potassium levels frequently in high-risk patients. 1

Choosing Between ACE Inhibitors and ARBs

When albuminuria is present and treatment is indicated:

• Both classes are equally effective for renal protection in diabetic kidney disease. 3, 4
• Choose based on tolerability rather than efficacy differences. 4
• Switch from ACE inhibitor to ARB only if persistent cough or angioedema develops. 3
• For type 1 diabetes with albuminuria, ACE inhibitors have the longest track record of evidence. 2
• For type 2 diabetes with macroalbuminuria, ARBs have the strongest evidence base. 2

Strength of Evidence

The most recent and highest quality guideline evidence comes from the American Diabetes Association, which has consistently stated since 2014 that ACE inhibitors or ARBs should not be prescribed to diabetic patients with normal blood pressure and normal albumin excretion. 2, 1 This recommendation is based on clinical trials showing no benefit in preventing diabetic kidney disease and one trial demonstrating increased cardiovascular events with ARB therapy in this population. 1