Do we prescribe ACE inhibitors (Angiotensin-Converting Enzyme inhibitors) or ARBs (Angiotensin II Receptor Blockers) to patients with diabetes without hypertension?

ACE Inhibitors and ARBs in Diabetic Patients Without Hypertension

Do not prescribe ACE inhibitors or ARBs to patients with diabetes who lack both hypertension and kidney disease, as clinical trials show no benefit in preventing diabetic kidney disease and one trial demonstrated increased cardiovascular events. 1

Clinical Decision Algorithm

The decision to prescribe ACE inhibitors or ARBs in diabetic patients without hypertension depends entirely on the presence and severity of kidney disease:

Step 1: Assess Kidney Function and Albuminuria

Measure spot urinary albumin-to-creatinine ratio (UACR) and eGFR in all diabetic patients annually. 2

Step 2: Apply Treatment Based on Kidney Status

No Kidney Disease (UACR <30 mg/g and eGFR ≥60 mL/min/1.73 m²)

• Do NOT prescribe ACE inhibitors or ARBs 1
• 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
• In type 1 diabetic patients without albuminuria or hypertension, ACE inhibitors or ARBs did not prevent the development of diabetic glomerulopathy on kidney biopsy 1
• In type 2 diabetic patients with normal urinary albumin excretion, an ARB actually increased the rate of cardiovascular events despite reducing albuminuria development 1, 2

Moderate Albuminuria (UACR 30-299 mg/g)

• Consider prescribing ACE inhibitor or ARB at maximum tolerated dose even without hypertension 1
• ACE inhibitor or ARB therapy reduces progression to more advanced albuminuria (≥300 mg/g) and cardiovascular events 1
• Important caveat: While these medications are often prescribed for albuminuria without hypertension, clinical trials have not been performed in this specific setting to determine whether this improves renal outcomes 1
• The evidence shows benefit for reducing albuminuria progression and cardiovascular events, but not for preventing end-stage renal disease 1

Severe Albuminuria (UACR ≥300 mg/g) and/or Reduced eGFR (<60 mL/min/1.73 m²)

• Strongly prescribe ACE inhibitor or ARB as first-line therapy regardless of blood pressure status 1, 2
• These medications reduce the risk of progression to end-stage kidney disease 1
• Use maximum tolerated dose indicated for blood pressure treatment 1
• ACE inhibitors and ARBs are considered to have similar benefits and risks; if one class is not tolerated, substitute the other 1

Critical Monitoring Requirements

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

Common Pitfalls to Avoid

• Never combine ACE inhibitors and ARBs 1, 3, 4

  • Two clinical trials found no benefits on cardiovascular or kidney disease outcomes 1
  • Combination therapy had higher adverse event rates including hyperkalemia and acute kidney injury 1, 3, 4
  • The VA NEPHRON-D trial specifically showed that patients with type 2 diabetes receiving losartan plus lisinopril experienced increased hyperkalemia and acute kidney injury without additional benefit 3

• Do not prescribe these medications solely for "cardioprotection" in diabetic patients without kidney disease or hypertension 1, 2

  • Absent kidney disease, ACE inhibitors or ARBs are not superior to thiazide-like diuretics or dihydropyridine calcium channel blockers 1

• Watch for hyperkalemia risk 1, 3, 4

  • Coadministration with potassium-sparing diuretics, NSAIDs, or in patients with reduced eGFR increases hyperkalemia risk 3, 4
  • Monitor serum potassium frequently in high-risk patients 1, 4

Evidence Quality Considerations

The strongest guideline evidence comes from the 2019 American Diabetes Association Standards of Medical Care 1 and the 2022 ADA Cardiovascular Disease guidelines 1, which consistently state that ACE inhibitors or ARBs are not recommended for patients without hypertension to prevent the development of chronic kidney disease. This recommendation is based on clinical trials showing lack of benefit in type 1 diabetes patients without albuminuria or hypertension 1 and potential harm (increased cardiovascular events) in type 2 diabetes patients with normal albumin excretion 1, 2.