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

From the Guidelines

In patients with type 2 diabetes mellitus (T2DM) and proteinuria, either an Angiotensin-Converting Enzyme Inhibitor (ACEI) or an Angiotensin Receptor Blocker (ARB) can be used as first-line therapy, as both medication classes have similar efficacy in reducing proteinuria and slowing progression of diabetic kidney disease. The choice between an ACEI or ARB often depends on individual patient factors such as tolerability and side effect profile, as noted in the 2022 consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) 1.

Some key points to consider when selecting between an ACEI and an ARB include:

• Common ACEIs include lisinopril (10-40 mg daily), ramipril (2.5-20 mg daily), and enalapril (5-40 mg daily)
• Common ARBs include losartan (50-100 mg daily), valsartan (80-320 mg daily), and irbesartan (150-300 mg daily)
• ACEIs are more commonly associated with a dry cough (occurring in 5-35% of patients) and angioedema, while ARBs generally have fewer side effects but may be more expensive
• When initiating either medication, start at a lower dose and titrate upward while monitoring blood pressure, serum potassium, and kidney function (serum creatinine) within 1-2 weeks of starting therapy and after dose increases, as recommended by the 2021 KDIGO clinical practice guideline for the management of glomerular diseases 1.

It's also important to note that combination therapy with both an ACEI and ARB is not recommended due to increased risk of adverse effects without significant additional benefit, as stated in the 2020 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD 1 and the 2022 ADA and KDIGO consensus report 1. Both medication classes work by blocking the renin-angiotensin-aldosterone system, which reduces intraglomerular pressure, decreases proteinuria, and provides renoprotective effects beyond blood pressure control alone.

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)

Both ACEI and ARB are generally considered effective for patients with T2DM and proteinuria, but the provided drug label specifically mentions the use of ARB (losartan) for the treatment of diabetic nephropathy with proteinuria in patients with T2DM and a history of hypertension 2.

• ARB is preferred in this context based on the label.
• However, it's essential to note that ACEI is also a common treatment for similar conditions, but the label does not directly compare the two.

From the Research

Comparison of ARB and ACEI for T2DM with Proteinuria

• Both Angiotensin-Converting Enzyme Inhibitors (ACEI) and Angiotensin Receptor Blockers (ARB) are used to manage patients with type 2 diabetes mellitus (T2DM) and proteinuria.
• Studies have shown that ARB can provide an efficacious treatment option for the prevention of renal disease progression in patients with hypertension and/or diabetes 3.
• ARB have been found to be better tolerated than ACEI and may be a more practical therapeutic option 3.
• Clinical studies have demonstrated the efficacy of irbesartan, losartan, telmisartan, and valsartan in the management of chronic kidney disease (CKD) 3.

Efficacy of ARB in Reducing Proteinuria

• ARB have been shown to reduce proteinuria in patients with T2DM and diabetic nephropathy 4, 5.
• The reduction of proteinuria with ARB is also linked to improved cardiovascular outcomes 3, 5.
• Telmisartan has been found to provide superior reductions in proteinuria compared to losartan, even when blood pressures are equalized with concomitant antihypertensives 3.

Comparison with ACEI

• ACEI have been found to reduce systemic blood pressure in hypertensive patients with diabetic and nondiabetic renal disease without causing dramatic changes in glomerular filtration rate or renal blood flow 6.
• However, the use of ACEI in progressive renal disease is still considered "innovative" therapy and has not been approved by the Food and Drug Administration (FDA) for this indication 6.
• ARB have been found to be equivalent to ACEI in preventing glomerular filtration rate decline and reducing proteinuria 7.

Renal Protection

• ARB can prevent or delay progression to end-stage renal disease independently of reductions in blood pressure 7.
• The blockade of the renin-angiotensin system beyond that required for maximum blood pressure reduction provides optimum renal protection 7.
• 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 5.