Should diabetic patients be treated with an Angiotensin-Converting Enzyme (ACE) inhibitor or an Angiotensin Receptor Blocker (ARB)?

Should Diabetic Patients Be on an ACE Inhibitor or ARB?

Diabetic patients should be on an ACE inhibitor or ARB only if they have hypertension (blood pressure ≥140/90 mmHg) or kidney disease (albuminuria with UACR ≥30 mg/g or eGFR <60 mL/min/1.73 m²), but these medications are not recommended for diabetic patients without these conditions. 1, 2

Clinical Decision Algorithm Based on Blood Pressure and Kidney Status

For Diabetic Patients WITH Hypertension:

• If blood pressure is ≥140/90 mmHg: Immediately initiate an ACE inhibitor or ARB as first-line therapy alongside lifestyle modifications 1, 3

• If blood pressure is 130-139/80-89 mmHg: Start lifestyle modifications (weight control, sodium reduction, increased physical activity, alcohol moderation) for a maximum of 3 months, then add an ACE inhibitor or ARB if blood pressure remains above target 1, 3

• Target blood pressure: Aim for <130/80 mmHg in most diabetic patients 1, 3

• Special consideration: ACE inhibitors or ARBs are specifically recommended as first-line therapy for diabetic patients with established coronary artery disease 1

For Diabetic Patients WITH Kidney Disease (Regardless of Blood Pressure):

• Severe albuminuria (UACR ≥300 mg/g) or reduced eGFR (<60 mL/min/1.73 m²): Strongly prescribe an ACE inhibitor or ARB at the maximum tolerated dose as first-line therapy, even without hypertension 1

• Moderate albuminuria (UACR 30-299 mg/g): Initiate an ACE inhibitor or ARB at maximum tolerated dose to reduce progression to more advanced albuminuria and cardiovascular events 1, 2

• No kidney disease (UACR <30 mg/g and eGFR ≥60 mL/min/1.73 m²): Do NOT prescribe ACE inhibitors or ARBs, as they provide no benefit and may increase cardiovascular events 1, 2

Critical Evidence Supporting This Approach

The American Diabetes Association explicitly states that ACE inhibitors or ARBs are not recommended for patients without hypertension to prevent the development of chronic kidney disease 1, 2. This recommendation is based on:

• A trial in type 2 diabetic patients with normal urinary albumin excretion showed an ARB actually increased cardiovascular events despite reducing albuminuria development 1, 2

• A trial in type 1 diabetic patients without albuminuria or hypertension found ACE inhibitors or ARBs did not prevent diabetic glomerulopathy on kidney biopsy 1, 2

• In the absence of kidney disease, ACE inhibitors or ARBs are not superior to thiazide-like diuretics or dihydropyridine calcium channel blockers for blood pressure control 1, 2

ACE Inhibitor vs. ARB: Which to Choose?

ACE inhibitors and ARBs are considered to have similar benefits and risks 1. The choice between them should be based on:

• Start with either an ACE inhibitor or ARB as both are equally effective 1

• If one class is not tolerated (e.g., dry cough with ACE inhibitors), substitute with the other class 1, 3, 4

• Both provide renoprotection beyond blood pressure-lowering effects 3

Multiple-Drug Therapy Considerations

Most diabetic patients with hypertension will require multiple antihypertensive medications to achieve blood pressure targets 1. When adding additional agents:

• Thiazide-like diuretics (chlorthalidone or indapamide preferred) should generally be one of the first two drugs used 1

• Dihydropyridine calcium channel blockers and beta-blockers are effective additions to ACE inhibitors or ARBs 1

• For blood pressure ≥160/100 mmHg: Initiate two antihypertensive medications simultaneously or use a single-pill combination 1

Critical Pitfalls to Avoid

Never Combine ACE Inhibitors and ARBs

Do not use ACE inhibitors and ARBs together 1, 5, 6. The VA NEPHRON-D trial demonstrated that combination therapy:

• Provided no additional benefit for kidney or cardiovascular outcomes 5
• Increased adverse events: hyperkalemia, syncope, and acute kidney injury 1, 5, 6

Never Combine with Direct Renin Inhibitors

Do not combine ACE inhibitors or ARBs with aliskiren in diabetic patients, as this increases risks of hypotension, hyperkalemia, and renal dysfunction without added benefit 1, 5, 6

Do Not Prescribe for "Cardioprotection" Without Indication

Avoid prescribing ACE inhibitors or ARBs solely for cardioprotection in diabetic patients without hypertension or kidney disease, as this practice lacks evidence and may cause harm 1, 2

Essential Monitoring Requirements

When prescribing ACE inhibitors or ARBs to diabetic patients:

• Monitor serum creatinine/eGFR and serum potassium within 2-4 weeks of initiation or dose changes, then at least annually 1, 2

• Watch for hyperkalemia risk, especially with:

  • Reduced eGFR 6
  • Concomitant potassium-sparing diuretics, potassium supplements, or salt substitutes 5, 6
  • NSAIDs (which can also cause acute kidney injury) 5, 6

• Screen all diabetic patients annually with spot urinary albumin-to-creatinine ratio (UACR) and eGFR to identify those who need ACE inhibitor or ARB therapy 1, 2

Strength of Evidence

The most recent and highest-quality guidelines come from the 2021 American Diabetes Association Standards of Medical Care 1 and the 2019 ADA Microvascular Complications guidelines 1, which consistently emphasize that ACE inhibitors or ARBs should be reserved for diabetic patients with specific indications (hypertension or kidney disease) rather than prescribed universally to all diabetic patients.