From the Guidelines
Empagliflozin (Jardiance) is currently considered the best SGLT2 inhibitor for heart protection, as it has shown the most robust cardiovascular benefits in clinical trials, particularly in reducing the risk of cardiovascular death and hospitalization for heart failure 1.
Key Points
- The standard dose of empagliflozin is 10mg once daily, which can be increased to 25mg daily if needed and tolerated.
- Dapagliflozin (Farxiga) is a close second choice, also with strong evidence for heart failure benefits.
- When starting any SGLT2 inhibitor, patients should be advised about potential side effects including genital yeast infections, urinary tract infections, and volume depletion.
- SGLT2 inhibitors work by increasing glucose excretion through the kidneys, but they also have direct beneficial effects on the heart and blood vessels independent of their glucose-lowering action.
Benefits of SGLT2 Inhibitors
- Reduce cardiac workload
- Improve ventricular loading conditions
- Have anti-inflammatory effects on the cardiovascular system
- Appropriate for patients with type 2 diabetes who have established cardiovascular disease or are at high risk for it
- Increasingly being used in non-diabetic patients specifically for heart failure management
Clinical Evidence
- The EMPA-REG OUTCOME trial showed that empagliflozin reduced the relative risk for hospitalization from heart failure by 35% 1.
- The CANVAS Program showed that canagliflozin reduced hospitalization from heart failure by 33% 1.
- The DAPA-HF study showed that dapagliflozin reduced cardiovascular mortality and hospitalization for heart failure by 17% 1.
From the FDA Drug Label
To reduce the risk of sustained eGFR decline, end stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression (1) To reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure. (1) To reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and either established cardiovascular disease or multiple cardiovascular risk factors (1)
The best Sodium-Glucose Cotransporter 2 (SGLT2) inhibitor for heart (cardiac) protection is dapagliflozin 2, as it has indications for reducing the risk of:
- cardiovascular death
- hospitalization for heart failure
- urgent heart failure visit in adults with heart failure, and also for reducing the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and either established cardiovascular disease or multiple cardiovascular risk factors. Empagliflozin 3 is only indicated to reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease.
From the Research
SGLT2 Inhibitors for Cardiac Protection
The following SGLT2 inhibitors have been studied for their effectiveness in cardiac protection:
- Empagliflozin: has been shown to reduce the risk of cardiovascular death or heart failure hospitalization in patients with chronic heart failure 4, 5
- Canagliflozin: has been shown to reduce the risk of major adverse cardiovascular events and hospitalization for heart failure 6
- Dapagliflozin: has been shown to reduce the risk of hospitalization for heart failure 6
Comparative Effectiveness of SGLT2 Inhibitors
A study comparing the effectiveness of canagliflozin, dapagliflozin, and empagliflozin found that:
- Empagliflozin and canagliflozin had comparable cardiovascular effectiveness at clinically effective doses 7
- Dapagliflozin had a higher risk of heart failure hospitalization, particularly at low doses 7
- Empagliflozin was found to be cost-effective compared to canagliflozin, dapagliflozin, and standard of care in patients with type 2 diabetes and established cardiovascular disease 6
Safety and Adverse Events
The safety and adverse event profiles of SGLT2 inhibitors have been studied, with findings including:
- Empagliflozin had a lower risk of genital infections and diabetic ketoacidosis compared to canagliflozin and dapagliflozin 7, 4
- Canagliflozin had a higher risk of severe urinary tract infections compared to empagliflozin 7
- Dapagliflozin had a lower risk of genital infections and diabetic ketoacidosis compared to canagliflozin 7