In patients with type 2 diabetes mellitus (T2DM) and proteinuria, which is preferred: Angiotensin-Converting Enzyme Inhibitor (ACEI) or Angiotensin Receptor Blocker (ARB)?

From the Guidelines

Both ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are effective first-line options for patients with type 2 diabetes mellitus and proteinuria, with neither class definitively preferred over the other. According to the most recent and highest quality study 1, ACE inhibitors and ARBs have been standard of care in patients with type 1 and type 2 diabetes and chronic kidney disease (CKD) for decades. The study recommends using either ACE inhibitors or ARBs as the preferred first-line agent for blood pressure treatment among patients with diabetes, hypertension, and albumin-to-creatinine ratio (ACR) ≥30 mg/g.

Some key points to consider when choosing between ACEIs and ARBs include:

• Common ACEIs include lisinopril (10-40 mg daily), enalapril (5-40 mg daily in divided doses), and ramipril (2.5-20 mg daily)
• Common ARBs include losartan (50-100 mg daily), valsartan (80-320 mg daily), and irbesartan (150-300 mg daily)
• Treatment should start at a lower dose and titrate upward while monitoring kidney function and potassium levels
• Both medication classes work by blocking the renin-angiotensin-aldosterone system, reducing intraglomerular pressure, decreasing proteinuria, and slowing kidney disease progression
• ACEIs may cause a dry cough in 5-20% of patients due to bradykinin accumulation, while ARBs typically don't cause this side effect
• If a patient develops a cough on an ACEI, switching to an ARB is recommended
• Both classes carry similar risks of hyperkalemia, acute kidney injury, and angioedema, and both are contraindicated during pregnancy
• The choice between them often depends on individual tolerability, cost considerations, and specific comorbidities.

It's also important to note that the combination of ACEIs and ARBs is not recommended due to the increased risk of adverse events, particularly hyperkalemia and acute kidney injury, as stated in the study 1.

From the FDA Drug Label

Treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria in patients with type 2 diabetes and a history of hypertension. ( 1.3)

In patients with type 2 diabetes mellitus (T2DM) and proteinuria, Angiotensin Receptor Blocker (ARB) is preferred, as indicated by the drug label for losartan, an ARB, which is used for the treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria in patients with type 2 diabetes and a history of hypertension 2.

• The label does not provide a direct comparison between ACEI and ARB in this specific patient population.
• However, it does mention that dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, suggesting that monotherapy with either an ACEI or an ARB may be preferred over combination therapy 2.

From the Research

Comparison of ACEI and ARB in Patients with T2DM and Proteinuria

• Both Angiotensin-Converting Enzyme Inhibitors (ACEI) and Angiotensin Receptor Blockers (ARB) are used in the treatment of patients with type 2 diabetes mellitus (T2DM) and proteinuria.
• According to the study 3, combination therapy with ACEI and ARB reduces proteinuria and prevents structural lesions more effectively than either drug alone in experimental diabetic and non-diabetic chronic kidney disease (CKD).
• The study 4 suggests that ARB induces favorable changes in systemic blood pressure, renal hemodynamics, and proteinuria similar to those induced by ACE inhibition, and the combination of ARB and ACE inhibition is well tolerated and even more effective than monotherapy in reducing systemic blood pressure and albuminuria in diabetic nephropathy.
• The study 5 indicates that ACE inhibitors effectively reduce systemic vascular resistance in patients with hypertension, heart failure, or chronic renal disease, and this antihypertensive efficacy probably accounts for an important part of their long-term renoprotective effects in patients with diabetic and non-diabetic renal disease.
• A meta-analysis 6 showed that the combination of ACEI and ARB was more effective than ACEI or ARB alone in reducing 24-hour proteinuria, systolic blood pressure, and diastolic blood pressure in patients with diabetic nephropathy.
• The study 7 demonstrates the efficacy of ARBs in the management of CKD, and all ARBs tested to date have proved effective in improving at least some aspects of renal dysfunction.

Preference between ACEI and ARB

• While both ACEI and ARB are effective in treating patients with T2DM and proteinuria, the studies suggest that the combination of ACEI and ARB may be more effective than monotherapy in reducing proteinuria and preventing renal disease progression.
• However, the choice between ACEI and ARB may depend on individual patient characteristics, such as tolerance to the medication and presence of other comorbidities.
• The study 4 suggests that ARB may be a more practical therapeutic option due to its better tolerability compared to ACEI.
• The study 7 indicates that telmisartan, an ARB, provides superior reductions in proteinuria to losartan, another ARB, possibly due to its higher receptor affinity, longer plasma half-life, and higher lipophilicity.