From the Guidelines
Empagliflozin, dapagliflozin, and canagliflozin are the SGLT2 inhibitors that have demonstrated cardiac benefits in patients with established cardiovascular disease, with empagliflozin reducing cardiovascular death by 38%, dapagliflozin demonstrating a 17% reduction in major adverse cardiovascular events and hospitalization for heart failure, and canagliflozin showing a 14% reduction in major adverse cardiovascular events, as supported by the most recent study 1. The SGLT2 inhibitors provide cardiovascular benefits through multiple mechanisms, including reduced blood pressure, decreased vascular stiffness, improved cardiac metabolism, and beneficial effects on cardiac remodeling. Some key points to consider when using these medications include:
- The typical starting doses are empagliflozin 10mg daily, dapagliflozin 10mg daily, and canagliflozin 100mg daily.
- Patients should be monitored for potential side effects, including genital mycotic infections, urinary tract infections, and volume depletion, particularly in elderly patients or those on diuretics.
- The use of SGLT2 inhibitors has been recommended in individuals with type 2 diabetes and asymptomatic stage B heart failure or with high risk of or established cardiovascular disease to reduce the risk of hospitalization for heart failure, as stated in the latest guidelines 1.
- The benefits of SGLT2 inhibitors in reducing the risk of worsening heart failure and cardiovascular death have been consistently demonstrated across multiple studies, including the EMPA-REG OUTCOME, CANVAS, and DECLARE-TIMI 58 trials, as referenced in 1 and 1.
From the FDA Drug Label
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. INVOKANA is a sodium-glucose co-transporter 2 (SGLT2) inhibitor indicated: ... To reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease
The SGLT2 inhibitors with demonstrated cardiac benefits in patients with established cardiovascular disease are:
- Empagliflozin 2, to reduce the risk of cardiovascular death
- Canagliflozin 3, to reduce the risk of major adverse cardiovascular events These SGLT2 inhibitors have shown benefits in reducing the risk of cardiovascular events in patients with type 2 diabetes mellitus and established cardiovascular disease.
From the Research
SGLT2 Inhibitors with Cardiac Benefits
The following SGLT2 inhibitors have demonstrated cardiac benefits in patients with established cardiovascular disease:
- Empagliflozin: has been shown to reduce the risk of cardiovascular death or heart failure hospitalization in patients with chronic heart failure 4, 5, 6
- Canagliflozin: has been found to reduce the risk of composite cardiovascular events in high-risk individuals with type 2 diabetes mellitus 5
- Dapagliflozin: has been shown to have comparable cardiovascular effectiveness to empagliflozin, although low-dose dapagliflozin may have a reduced benefit for heart failure hospitalization 7
- Ertugliflozin: is also an SGLT2 inhibitor, but its cardiac benefits are not as well-studied as those of empagliflozin, canagliflozin, and dapagliflozin 4
Mechanisms of Cardiac Benefits
The exact mechanisms by which SGLT2 inhibitors exert their cardiac benefits are not fully understood, but may involve:
- Multiple metabolic and hemodynamic mechanisms 4
- Reductions in blood glucose levels, body weight, and blood pressure 5, 8
- Improvement in renal outcomes 5
Clinical Use of SGLT2 Inhibitors
SGLT2 inhibitors 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. The dose of insulin or sulfonylureas may need to be lowered when used with SGLT2 inhibitors to reduce the risk of hypoglycemia 5.