Would it be appropriate to add lisinopril to a patient with hypertension and diabetes mellitus type 2, currently taking metformin (Metformin) 500 mg twice daily (BID) and amlodipine (Amlodipine) 5 mg once daily, with persistent hypertension?

From the Guidelines

Adding lisinopril to the patient's current regimen of metformin and amlodipine is a reasonable approach to manage persistent hypertension, as ACE inhibitors like lisinopril provide renoprotective effects beyond blood pressure control, particularly beneficial in patients with diabetes 1. The patient's blood pressure remains elevated in the 140-150s systolic range while taking amlodipine 5 mg daily and metformin 500 mg twice daily for diabetes. According to the 2017 American College of Cardiology/American Heart Association hypertension guideline, antihypertensive drug treatment should be initiated at a BP of 130/80 mm Hg or higher in adults with DM, and the treatment goal should be less than 130/80 mm Hg 1. Some key points to consider when initiating lisinopril include:

• Starting with a dose of 10 mg once daily and monitoring blood pressure response, with potential titration up to 20-40 mg daily if needed
• Monitoring renal function and potassium levels within 1-2 weeks of starting therapy, as ACE inhibitors can affect both parameters
• Counseling the patient about potential side effects, including dry cough and the rare but serious risk of angioedema
• Considering substitution with an angiotensin receptor blocker (ARB) if a cough develops The combination therapy of a calcium channel blocker (amlodipine) and an ACE inhibitor (lisinopril) offers complementary mechanisms of action, with amlodipine causing vasodilation and lisinopril blocking the renin-angiotensin-aldosterone system. This approach is supported by the British Hypertension Society guidelines, which recommend initiating antihypertensive drug therapy if sustained systolic blood pressure is ≥ 140 mm Hg or sustained diastolic blood pressure is ≥ 90 mm Hg in people with diabetes mellitus 1. Additionally, the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) compared the effectiveness of an ACE inhibitor (lisinopril) versus a calcium-channel blocker (amlodipine) versus a thiazide diuretic (chlorthalidone) as first-line therapy for mild to moderate hypertension, and found no differences between treatments in primary outcome or all-cause mortality 1. However, the most recent and highest quality study, the 2017 American College of Cardiology/American Heart Association hypertension guideline, recommends initiating antihypertensive drug therapy at a BP of 130/80 mm Hg or higher in adults with DM, and the treatment goal should be less than 130/80 mm Hg 1. Therefore, adding lisinopril to the patient's current regimen is a reasonable approach to manage persistent hypertension, with careful monitoring of blood pressure, renal function, and potential side effects 1.

From the FDA Drug Label

The dose-dependent antihypertensive effect of lisinopril was consistent across several demographic subgroups: age, Tanner stage, gender, and race In two placebo controlled, 12-week clinical studies compared the addition of lisinopril up to 20 mg daily to digitalis and diuretics alone. The combination of lisinopril, digitalis and diuretics reduced the following signs and symptoms of heart failure: edema, rales, paroxysmal nocturnal dyspnea and jugular venous distention

Lisinopril can be used to treat hypertension. The patient in question has hypertension and diabetes mellitus type 2, and is currently taking metformin and amlodipine.

• The drug label does not directly address the use of lisinopril in patients with diabetes mellitus type 2 who are taking metformin and amlodipine.
• However, it does mention the antihypertensive effect of lisinopril and its use in combination with other medications, such as digitalis and diuretics.
• Given the patient's persistent hypertension, adding lisinopril to their treatment regimen may be considered, but it is essential to monitor their blood pressure, renal function, and potential interactions with their current medications 2.

From the Research

Patient Profile

• The patient has hypertension and diabetes mellitus type 2
• Currently taking metformin (Metformin) 500 mg twice daily (BID) and amlodipine (Amlodipine) 5 mg once daily
• Persistent hypertension despite current medication

Considerations for Adding Lisinopril

• Studies have shown that adding an angiotensin-converting enzyme (ACE) inhibitor, such as lisinopril, to a patient's regimen can be effective in reducing blood pressure 3, 4, 5
• The combination of lisinopril and amlodipine has been shown to be safe and effective in patients with hypertension and diabetes 4, 5
• Lisinopril has been found to have a cardio-nephroprotective effect, which is important for patients with diabetes and hypertension 5

Potential Benefits of Adding Lisinopril

• Reduced blood pressure 3, 4, 5
• Improved cardiovascular and renal outcomes 4, 5
• Metabolically neutral, meaning it will not negatively impact the patient's diabetes management 5

Studies Supporting the Use of Lisinopril in Similar Patient Populations

• A study published in 2008 found that adding amlodipine to patients with hypertension and diabetes who were already taking an ACE inhibitor or angiotensin receptor blocker resulted in improved blood pressure control 3
• A study published in 2022 found that the combination of lisinopril and amlodipine was effective in reducing blood pressure and improving cardiovascular and renal outcomes in patients with hypertension and arteriosclerosis obliterans 4
• A study published in 2015 found that long-term combined therapy with lisinopril and amlodipine resulted in significant reductions in blood pressure, left ventricular mass, and albuminuria, as well as improved metabolic parameters and reduced insulin resistance 5