Why are Angiotensin-Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARB) used to treat hypertension in patients with Type 2 Diabetes Mellitus?

From the Guidelines

ACE inhibitors and ARBs are the preferred first-line treatments for hypertension in patients with type 2 diabetes due to their dual benefits of lowering blood pressure and providing kidney protection. These medications not only effectively reduce blood pressure but also decrease the progression of kidney disease in patients with albuminuria, as evidenced by the study published in Circulation in 2020 1. The study highlights the importance of ACE inhibitors and ARBs in reducing the risk of myocardial infarction, stroke, and cardiovascular death in patients with type 2 diabetes and coronary artery disease.

The mechanism by which ACE inhibitors and ARBs provide kidney protection is by blocking the renin-angiotensin-aldosterone system, which helps prevent diabetic kidney disease progression. Additionally, these medications have favorable metabolic profiles and do not negatively impact glycemic control or lipid levels. The American Diabetes Association guidelines, as updated in 2025 1, recommend ACE inhibitors or ARBs as the preferred first-line agents for blood pressure treatment among people with diabetes, hypertension, and chronic kidney disease.

Key benefits of ACE inhibitors and ARBs include:

• Reduction in blood pressure
• Decrease in the progression of kidney disease
• Reduction in the risk of myocardial infarction, stroke, and cardiovascular death
• Favorable metabolic profiles
• No negative impact on glycemic control or lipid levels

For most patients, starting doses would be lisinopril 10mg daily or losartan 50mg daily, titrating up as needed for blood pressure control. ACE inhibitors are typically tried first, with ARBs reserved for patients who develop a cough from ACE inhibitors. Regular monitoring of kidney function and potassium levels is necessary when starting these medications, especially in patients with existing kidney disease. A blood pressure level <130/80 mmHg is recommended to reduce cardiovascular disease mortality and slow chronic kidney disease progression among all people with diabetes 1.

From the FDA Drug Label

Losartan is indicated for the treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria (urinary albumin to creatinine ratio ≥300 mg/g) in patients with type 2 diabetes and a history of hypertension In this population, losartan reduces the rate of progression of nephropathy as measured by the occurrence of doubling of serum creatinine or end stage renal disease (need for dialysis or renal transplantation) The RENAAL study was a randomized, placebo-controlled, double-blind, multicenter study conducted worldwide in 1513 patients with type 2 diabetes with nephropathy Treatment with losartan resulted in a 16% risk reduction in the primary endpoint of doubling of serum creatinine, end-stage renal disease, or death Losartan also reduced the occurrence of sustained doubling of serum creatinine by 25% and ESRD by 29% as separate endpoints

ACE inhibitors and ARB's are used to treat hypertension in patients with Type 2 Diabetes Mellitus because they have been shown to:

• Reduce the risk of stroke and cardiovascular events
• Slow the progression of nephropathy and reduce the risk of end-stage renal disease
• Provide renal protection by reducing proteinuria and slowing the decline in glomerular filtration rate This is based on the results of studies such as the RENAAL study 2, which demonstrated the benefits of losartan in patients with type 2 diabetes and nephropathy.

From the Research

Rationale for Using ACE Inhibitors and ARBs in Hypertensive Type 2 Diabetic Patients

• The renin-angiotensin-aldosterone system (RAAS) plays a crucial role in regulating blood pressure, and its dysregulation can lead to hypertension and cardiovascular diseases 3.
• ACE inhibitors and ARBs are used to treat hypertension in patients with Type 2 Diabetes Mellitus due to their ability to block the RAAS, providing benefits beyond blood pressure control 4, 5, 6, 7, 3.
• The use of ACE inhibitors in hypertensive Type 2 diabetic patients is supported by theoretical assumptions and results from recent major clinical trials, which suggest that ACE inhibitors have a superior antiproteinuric effect and may be more nephroprotective than other agents 4.

Clinical Trials and Studies

• The CAPPP, FACET, ABCD, and HOPE studies reported superior outcomes in patients treated with ACEI-based antihypertensive regimens compared with non-ACEI-based treatments in reducing the risk of macrovascular disease and micro- and macrovascular complications in Type 2 diabetes 4.
• The UKPDS 38 and HOT studies suggested that the degree of reduction of blood pressure, rather than the choice of a particular class of antihypertensive agent, is associated with decreased risk of cardiovascular events 4.
• The GUARD and ACCOMPLISH trials showed that ACE inhibitor plus calcium channel blocker combination therapy may be particularly useful in reducing cardiovascular outcomes in high-risk patients 5.
• The ALLHAT and VALUE trials demonstrated that diuretics and ARBs have a better hypotensive effect and are more successful in preventing many aspects of cardiovascular disease compared with CCBs and ACE inhibitors 6, 7.

Recommendations and Guidelines

• The 2024 Egyptian Cardiology Expert Consensus recommends ACE inhibitors as the first choice for reducing the risk of MI, primary prevention of HF, and secondary prevention of stroke, as well as for patients with Type 2 diabetes for BP control and primary prevention of diabetic kidney disease 3.
• The consensus group also recommends the use of ACE inhibitors and ARBs for the primary and secondary prevention of cardiovascular outcomes and stroke, highlighting the importance of effective BP control and RAAS blockade 3.