What are the recommended cardio/renal protective medications for patients with diabetes?

From the Guidelines

For patients with diabetes, SGLT-2 inhibitors, such as empagliflozin or dapagliflozin, are strongly recommended for cardio-renal protection, as they have been shown to reduce heart failure hospitalizations, cardiovascular events, and kidney disease progression, regardless of glucose control needs. The most recent and highest quality study, 1, demonstrated the significant benefits of dapagliflozin in reducing the risk of cardiovascular and kidney outcomes, with a hazard ratio of 0.61 for the primary endpoint. Additionally, the EMPA-KIDNEY study, also referenced in 1, showed that empagliflozin-treated participants had a lower risk of progression of kidney disease and death from cardiovascular causes. Other medications, such as GLP-1 receptor agonists, may also provide cardiovascular benefits, particularly for atherosclerotic disease. Key points to consider when selecting cardio-renal protective medications for patients with diabetes include:

• SGLT-2 inhibitors, such as empagliflozin 10-25 mg daily or dapagliflozin 5-10 mg daily, for their ability to reduce heart failure hospitalizations, cardiovascular events, and kidney disease progression
• GLP-1 receptor agonists, such as semaglutide 0.5-1 mg weekly or dulaglutide 0.75-4.5 mg weekly, for their cardiovascular benefits, particularly for atherosclerotic disease
• ACE inhibitors or ARBs, such as lisinopril 10-40 mg daily or losartan 50-100 mg daily, for their ability to reduce blood pressure, decrease albuminuria, and slow kidney disease progression, as recommended in 1
• Statins, for their essential role in cardiovascular protection. Treatment should be individualized based on comorbidities, kidney function, and cardiovascular risk profile.

From the FDA Drug Label

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 2 and 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 100 mg significantly reduced the risk of the primary composite endpoint based on a time-to-event analysis [HR: 0.70; 95% CI: 0.59,0.82; p<0.0001] Canagliflozin 100 mg also significantly reduced the risk of hospitalization for heart failure [HR: 0.61; 95% CI: 0.47 to 0.80; p<0.001]

The recommended cardio/renal protective medication for patients with diabetes is canagliflozin.

• Key benefits of canagliflozin include:
  • Reduced risk of major adverse cardiovascular events (MACE)
  • Reduced risk of end-stage kidney disease (ESKD), doubling of serum creatinine, and renal or CV death
  • Reduced risk of hospitalization for heart failure 2

From the Research

Cardio/Renal Protective Diabetes Medications

The following medications have been shown to have cardio/renal protective effects in patients with diabetes:

• SGLT2 inhibitors, such as empagliflozin, dapagliflozin, and canagliflozin, which have been found to reduce the risk of cardiovascular events, hospitalization for heart failure, and progression to end-stage kidney disease 3, 4, 5
• GLP-1 receptor agonists, which have been shown to reduce the risk of major cardiovascular events, admission to hospital for heart failure, and cardiovascular and all-cause mortality 6, 7

Recommended Medications

Based on the available evidence, the following medications are recommended for cardio/renal protection in patients with diabetes:

• Empagliflozin, which has been approved by the FDA for the reduction of cardiovascular death in adults with type 2 diabetes and cardiovascular disease 4
• SGLT2 inhibitors, which should be considered in patients with established cardiovascular disease, usually in combination with other glucose-lowering medications, when satisfactory glycemic control has not been achieved 5
• GLP-1 receptor agonists, which should be considered in patients at high risk of, or with established, cardiovascular disease 6

Patient Selection

When selecting patients for cardio/renal protective diabetes medications, the following factors should be considered:

• Presence of established cardiovascular disease or high risk of cardiovascular events 4, 5
• Presence of chronic kidney disease or high risk of progression to end-stage kidney disease 7
• Glycemic control and need for additional glucose-lowering medications 5
• Potential side effects and contraindications, such as increased risk of genitourinary infections, diabetic ketoacidosis, and bone fractures 3, 5