When to use Angiotensin-Converting Enzyme (ACE) inhibitor in patients with Diabetes Mellitus?

From the Guidelines

ACE inhibitors should be used as first-line therapy in diabetic patients with hypertension, particularly when there is evidence of kidney damage (albumin-to-creatinine ratio ≥30 mg/g) or when cardiovascular protection is needed. This recommendation is based on the strongest and most recent evidence from the 2020 KDIGO clinical practice guideline, which suggests that treatment with an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ARB) be initiated in patients with diabetes, hypertension, and albuminuria, and that these medications be titrated to the highest approved dose that is tolerated 1.

The use of ACE inhibitors in diabetic patients has been shown to slow the progression of kidney disease and reduce cardiovascular events, making them a crucial component of diabetes management 1. Common ACE inhibitors include lisinopril (10-40 mg daily), enalapril (5-40 mg daily in divided doses), and ramipril (2.5-20 mg daily). These medications work by blocking the conversion of angiotensin I to angiotensin II, reducing blood pressure and providing renoprotective effects by decreasing intraglomerular pressure and proteinuria.

Some key considerations when using ACE inhibitors in diabetic patients include:

• Monitoring kidney function and potassium levels regularly, especially when initiating therapy or adjusting doses 1
• Using caution in patients with advanced kidney disease (eGFR <30 ml/min/1.73m²) 1
• Avoiding combination therapy with ACEis and ARBs, as it can be harmful 1
• Considering the use of mineralocorticoid receptor antagonists, such as spironolactone and eplerenone, for resistant hypertension 1

Overall, the use of ACE inhibitors in diabetic patients with hypertension, albuminuria, or established cardiovascular disease is a crucial component of diabetes management, and should be guided by the most recent and strongest evidence available.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Indications for ACE Inhibitors in Diabetes

• ACE inhibitors are recommended as a first-line agent for reducing blood pressure and preventing or attenuating nephropathy in hypertensive diabetic patients with IDDM or NIDDM and microalbuminuria or overt renal disease 2
• They can also be used in normotensive patients with microalbuminuria and IDDM, as shown by the EUCLID study 2
• The use of ACE inhibitors in patients with normoalbuminuria is not well established, and more research is needed to determine their effectiveness in this population 2

Benefits of ACE Inhibitors in Diabetes

• ACE inhibitors have been shown to lower blood pressure and produce a renoprotective effect in patients with IDDM and NIDDM without detriment to glycaemic control or lipid profiles 2
• They may also have beneficial effects on retinopathy, as shown by the EUCLID study, which found that lisinopril slowed the progression of retinopathy in patients with IDDM 2
• ACE inhibitors may also improve neurological function, although this finding is preliminary 2
• The combination of an ACE inhibitor and an angiotensin II receptor blocker (ARB) may provide superior blood pressure and albumin excretion rate control than either monotherapy in patients with type 2 diabetes, hypertension, and microalbuminuria 3

Considerations for Initiating ACE Inhibitors in Diabetes

• The dose of ACE inhibitors should be lower in patients with renal impairment, unless an agent that is not excreted by the kidneys is chosen 4
• The dose should be titrated up to the maximum tolerated to optimize end-organ protection, and intermediate-acting agents should be given in a twice-daily divided dose when higher doses are used 4
• Electrolytes should be checked before commencing ACE inhibitors, 1-2 weeks later, and after each dose increment 4
• A modest decrease in estimated glomerular filtration rate (eGFR) and increase in creatinine often occurs with ACE inhibitors, and the agents may need to be discontinued if eGFR decreases by >15%, if creatinine increases by >20%, or if hyperkalemia develops 4

Comparison of ACE Inhibitors and ARBs in Diabetes

• ARBs may be preferred over ACE inhibitors for diabetic patients with albuminuria, as they have been shown to reduce the risk of end-stage renal disease (ESRD) and doubling of the serum creatinine level 5
• Both ACE inhibitors and ARBs have been shown to reduce the risk of doubling of the serum creatinine level, but only ARBs have been shown to reduce the risk of ESRD 5
• ACE inhibitors and ARBs have not been shown to reduce all-cause mortality or cardiovascular events in patients with diabetes and albuminuria 5