From the Guidelines
For a patient with diabetes mellitus (DM), chronic kidney disease (CKD), and congestive heart failure (CHF), empagliflozin or dapagliflozin would be the best SGLT2 inhibitor choices, as they have been shown to reduce cardiovascular death, hospitalization for heart failure, and slow kidney disease progression, with benefits seen even at eGFR levels as low as 20 mL/min/1.73m² 1.
Key Considerations
- Empagliflozin (Jardiance) 10mg daily and dapagliflozin (Farxiga) 10mg daily are both effective options for patients with DM, CKD, and CHF, with similar benefits in reducing cardiovascular and renal outcomes 1.
- These medications work by blocking glucose reabsorption in the kidneys, promoting glucose excretion in urine, but their cardio-renal benefits appear independent of their glucose-lowering effects, and are thought to be due to their ability to reduce preload and afterload on the heart, decrease inflammation, and improve energy metabolism in cardiac cells 1.
- Common side effects include genital mycotic infections and volume depletion, so patients should be counseled about proper genital hygiene and monitored for hypotension, especially if taking diuretics concurrently 1.
Evidence Summary
- The most recent guidelines recommend the use of SGLT2 inhibitors, such as empagliflozin and dapagliflozin, in patients with type 2 diabetes and CKD, with eGFR ≥20 mL/min/1.73m², to reduce CKD progression and cardiovascular events 1.
- The CREDENCE trial demonstrated that canagliflozin, another SGLT2 inhibitor, may be used with benefit down to an eGFR of 30 mL/min/1.73m², but empagliflozin and dapagliflozin have been shown to be effective at even lower eGFR levels 1.
- The EMPEROR-Preserved and EMPEROR-Reduced trials also demonstrated the efficacy of empagliflozin in patients with heart failure, with benefits seen at eGFR levels as low as 20 mL/min/1.73m² 1.
From the FDA Drug Label
INVOKANA is a sodium-glucose co-transporter 2 (SGLT2) inhibitor indicated: ... To reduce the risk of end-stage kidney disease, doubling of serum creatinine, cardiovascular death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria ( 1). JARDIANCE is a sodium-glucose co-transporter 2 (SGLT2) inhibitor indicated: ... to reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease. (1)
Based on the provided drug labels, canagliflozin appears to be the best SGLT2 inhibitor for a patient with DM, CKD, and CHF because it is indicated to reduce the risk of:
- End-stage kidney disease
- Doubling of serum creatinine
- Cardiovascular death
- Hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria 2. In contrast, empagliflozin is indicated to reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease, but it does not have specific indications for CKD or hospitalization for heart failure 3.
From the Research
SGLT2 Inhibitors for Patients with DM, CKD, and CHF
- SGLT2 inhibitors, such as empagliflozin, have been shown to be effective in reducing the risk of cardiovascular and kidney outcomes in patients with type 2 diabetes mellitus and established cardiovascular disease 4, 5.
- Empagliflozin has been found to reduce the risk of hospitalization for heart failure and mortality in patients with heart failure, regardless of left ventricular ejection fraction 6.
- The effects of empagliflozin on kidney outcomes have been found to be consistent across subgroups of patients with different levels of kidney function and albuminuria 4, 5.
- SGLT2 inhibitors have been shown to have positive effects on blood pressure, weight, and energy metabolism in the heart and kidneys, and may slow the progression of chronic kidney disease 7, 8.
Benefits of Empagliflozin
- Empagliflozin has been found to reduce the risk of cardiovascular death, hospitalization for heart failure, and all-cause mortality in patients with type 2 diabetes mellitus and established cardiovascular disease 4.
- Empagliflozin has been shown to improve kidney outcomes, including reducing the risk of incident or worsening nephropathy and slowing the progression of chronic kidney disease 5.
- Empagliflozin has a favorable safety profile, with minimal drug-drug interactions and no significant reduction in blood pressure 6.
Comparison of SGLT2 Inhibitors
- SGLT2 inhibitors, as a class, have been found to have similar benefits and risks, including reducing the risk of cardiovascular and kidney outcomes, and improving blood pressure and weight 7, 8.
- Empagliflozin has been found to have a unique pharmacological profile, with effects on hemodynamic, neurohumoral, metabolic, and vascular endothelial pathways influencing cardiac and renal disease 8.