From the Guidelines
Both Angiotensin Receptor Blockers (ARBs) and Angiotensin-Converting Enzyme (ACE) inhibitors are effective first-line treatments for patients with diabetes, particularly those with hypertension, albuminuria, or diabetic kidney disease, with the most recent evidence suggesting their equal efficacy in reducing morbidity, mortality, and improving quality of life 1.
Key Considerations
- ACE inhibitors (like lisinopril, ramipril, and enalapril) have historically been preferred as first-line agents, but ARBs (such as losartan, valsartan, and candesartan) are equally effective alternatives, especially for patients who experience ACE inhibitor-induced cough.
- Both medication classes provide similar benefits in reducing blood pressure, protecting kidney function, and decreasing cardiovascular events in diabetic patients.
- They work by blocking the renin-angiotensin-aldosterone system, though through different mechanisms - ACE inhibitors prevent the formation of angiotensin II while ARBs block its receptor.
- The typical starting doses are moderate (e.g., lisinopril 10mg daily or losartan 50mg daily) with gradual titration based on blood pressure response and kidney function.
- Regular monitoring of blood pressure, kidney function, and potassium levels is essential with either medication class.
- The choice between an ARB or ACE inhibitor should be individualized based on patient-specific factors including tolerance, cost considerations, and comorbidities.
Evidence Summary
- Studies have shown that ACE inhibitors and ARBs are effective in slowing the progression of kidney disease characterized by microalbuminuria in hypertensive patients with type 1 or type 2 diabetes 1.
- The Losartan Intervention for Endpoint Reduction (LIFE) study demonstrated the renoprotective properties of ARBs and their benefit in reducing cardiovascular events in diabetic patients 1.
- More recent guidelines suggest that ACE inhibitors or ARBs are not recommended for patients without hypertension to prevent the development of CKD, and the combined use of ACE inhibitors and ARBs should be avoided due to higher adverse event rates 1.
From the FDA Drug Label
The Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial enrolled 1448 patients with type 2 diabetes, elevated urinary-albumin-to-creatinine ratio, and decreased estimated glomerular filtration rate (GFR 30 to 89.9 mL/min), randomized them to lisinopril or placebo on a background of losartan therapy and followed them for a median of 2. 2 years. Patients receiving the combination of losartan and lisinopril did not obtain any additional benefit compared to monotherapy for the combined endpoint of decline in GFR, end stage renal disease, or death, but experienced an increased incidence of hyperkalemia and acute kidney injury compared with the monotherapy group
The efficacy of Angiotensin Receptor Blockers (ARBs) versus Angiotensin-Converting Enzyme (ACE) inhibitors for patients with diabetes is similar, as shown in the VA NEPHRON-D trial, where patients receiving losartan (an ARB) and lisinopril (an ACE inhibitor) did not obtain any additional benefit compared to monotherapy for the combined endpoint of decline in GFR, end stage renal disease, or death 2. However, the combination of ARBs and ACE inhibitors is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, including acute renal failure, compared to monotherapy 2.
- Key points:
- Similar efficacy between ARBs and ACE inhibitors for patients with diabetes
- Increased risk of adverse effects with combination therapy
- Monitor blood pressure, renal function, and electrolytes in patients on ARBs and ACE inhibitors
- Main considerations:
- Hyperkalemia and acute kidney injury are potential risks with combination therapy
- Losartan and lisinopril have similar efficacy in patients with diabetes, but combination therapy may not provide additional benefits 2
From the Research
Efficacy of ARBs vs ACEs for Diabetes
- The efficacy of Angiotensin Receptor Blockers (ARBs) versus Angiotensin-Converting Enzyme (ACE) inhibitors for patients with diabetes has been studied in various clinical trials 3, 4, 5, 6, 7.
- ACE inhibitors have been shown to reduce the progression of renal disease in patients with diabetes, and are considered the drug of choice for patients with type 1 diabetes mellitus and evidence of incipient or overt nephropathy 3, 4.
- ARBs have also been shown to reduce microalbuminuria compared with placebo, and are a viable choice for patients with type 2 diabetes mellitus and evidence of proteinuria 3, 5.
- The optimal dosage of ACE inhibitors or ARBs required to slow the progression of renal disease or impair the development of cardiovascular risk is not known, but data from many studies strongly support the use of higher doses to reduce proteinuria 5.
- ACE inhibitors have been reported to improve kidney, heart, and to a lesser extent, eye and peripheral nerve function of patients with diabetes mellitus, and have a specific 'organ-protective' effect beyond their antihypertensive properties 6.
- The use of ACE inhibitors has also been shown to reduce cardiovascular disease mortality and morbidity in high-risk persons, such as those with diabetes mellitus, even in the absence of renal disease 7.
Comparison of ARBs and ACEs
- Both ARBs and ACE inhibitors are effective in reducing blood pressure and proteinuria in patients with diabetes, but ACE inhibitors are still considered the drug of choice for patients with type 1 diabetes mellitus and evidence of incipient or overt nephropathy 3, 4.
- ARBs may be a viable alternative for patients who experience adverse events with ACE inhibitors, such as dry cough 3.
- The choice between ARBs and ACE inhibitors should be based on individual patient characteristics and clinical presentation, and both classes of drugs should be considered first-line therapy for patients with type 2 diabetes mellitus and nephropathy 3, 5.