What medications are effective for patients with hypertension and diabetes to protect the kidneys and heart?

From the Guidelines

For patients with hypertension and diabetes, ACE inhibitors (like lisinopril 10-40 mg daily or enalapril 5-40 mg daily) or ARBs (such as losartan 25-100 mg daily or valsartan 80-320 mg daily) are the most effective medications to protect both the kidneys and heart, as supported by the most recent guidelines 1. These medications reduce blood pressure while also providing specific renal protection by decreasing pressure within the kidney's filtering units and reducing protein leakage. For optimal heart and kidney protection, these should be combined with an SGLT-2 inhibitor (like empagliflozin 10-25 mg daily, dapagliflozin 5-10 mg daily, or canagliflozin 100-300 mg daily), which reduces cardiovascular events, heart failure hospitalizations, and slows kidney disease progression, as demonstrated in recent studies 1. Many patients will also need additional blood pressure medications to reach target levels below 130/80 mmHg, such as calcium channel blockers (amlodipine 5-10 mg daily) or thiazide diuretics (hydrochlorothiazide 12.5-25 mg daily). Regular monitoring of kidney function and potassium levels is essential, especially when starting these medications, with blood tests recommended at 2-4 weeks after initiation and dose changes, then every 3-6 months thereafter. Key considerations in the management of hypertension and diabetes include:

• The use of ACE inhibitors or ARBs as first-line therapy for hypertension in patients with diabetes, particularly in the presence of albuminuria or coronary artery disease 1
• The addition of SGLT-2 inhibitors for patients with established cardiovascular disease or at high risk of cardiovascular events 1
• The importance of achieving blood pressure targets below 130/80 mmHg to reduce the risk of cardiovascular and renal complications 1
• The need for regular monitoring of kidney function and potassium levels to minimize the risk of adverse effects from these medications.

From the FDA Drug Label

The CANVAS and CANVAS-R trials were multicenter, multi-national, randomized, double-blind parallel group, with similar inclusion and exclusion criteria... The integrated analysis of the CANVAS and CANVAS-R trials compared the risk of Major Adverse Cardiovascular Event (MACE) between canagliflozin and placebo when these were added to and used concomitantly with standard of care treatments for diabetes and atherosclerotic cardiovascular disease The primary endpoint, MACE, was the time to first occurrence of a three-part composite outcome which included cardiovascular death, non-fatal myocardial infarction and non-fatal stroke. The estimated hazard ratio (95% CI) for time to first MACE was 0.86 (0.75,0. 97). The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation Trial (CREDENCE) was a multinational, randomized, double-blind, placebo-controlled trial comparing canagliflozin with placebo in adult patients with type 2 diabetes mellitus, an eGFR ≥ 30 to < 90 mL/min/1. 73 m 2and albuminuria (urine albumin/creatinine > 300 to ≤ 5,000 mg/g) who were receiving standard of care including a maximum-tolerated, labeled daily dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB)

Canagliflozin is effective for patients with hypertension and diabetes to protect the kidneys and heart.

• The CANVAS and CANVAS-R trials showed that canagliflozin reduced the risk of Major Adverse Cardiovascular Events (MACE).
• The CREDENCE trial demonstrated the effectiveness of canagliflozin in patients with diabetic nephropathy and albuminuria. 2

From the Research

Medications for Patients with Hypertension and Diabetes

To protect the kidneys and heart in patients with hypertension and diabetes, several medications have been found to be effective. These include:

• SGLT2 inhibitors, which have been shown to reduce blood pressure, mortality, and cardiovascular disease, and slow the loss of glomerular filtration rate 3, 4
• Thiazide diuretics, such as chlortalidone and hydrochlorothiazide, which have been found to be effective in reducing mortality and the incidence of stroke 5
• ACE inhibitors, such as lisinopril, which have been shown to have favourable effects on hypertension and diabetic nephropathy 6
• Angiotensin II receptor blockers (ARBs), such as telmisartan, which have been found to have beneficial effects on blood pressure and albumin excretion rate when used in combination with ACE inhibitors 6

Mechanisms of Action

The mechanisms of action of these medications include:

• Inhibition of the coupled reabsorption of sodium and glucose from the proximal tubules, increasing renal glucose and sodium excretion 3, 4
• Inhibition of the sodium:proton exchanger, increasing the delivery of sodium to the loop of Henle and activating the tubuloglomerular feedback response to correct glomerular hyperfiltration 4
• Blockade of the renin-angiotensin system, reducing blood pressure and preserving kidney function 6

Clinical Outcomes

Clinical outcomes of these medications have been studied in several trials, including:

• The ALLHAT trial, which found no significant difference in relative risk for fatal coronary heart disease or nonfatal myocardial infarction between participants assigned to amlodipine, lisinopril, or chlorthalidone 7
• The study by 6, which found that dual blockade with lisinopril and telmisartan provided superior blood pressure and albumin excretion rate control than either monotherapy in patients with type 2 diabetes, hypertension, and microalbuminuria.