From the Guidelines
SGLT2 inhibitors significantly reduce cardiovascular risk in patients with type 2 diabetes as a class effect, and should be used to prevent the development of incident heart failure in patients with increased cardiovascular risk or established cardiovascular disease. The most recent evidence from the 2025 standards of care in diabetes 1 supports the use of SGLT2 inhibitors in reducing cardiovascular disease and heart failure outcomes in people with diabetes. Key benefits of SGLT2 inhibitors include:
- Reducing the relative risk for hospitalization from heart failure by 35% 1
- Lowering blood pressure (typically by 3-5 mmHg systolic)
- Promoting weight loss (average 2-3 kg)
- Decreasing inflammation
- Improving cardiac energy metabolism
- Reducing arterial stiffness Medications in this class include empagliflozin (Jardiance), canagliflozin (Invokana), dapagliflozin (Farxiga), and ertugliflozin (Steglatro), typically taken once daily. These medications work by preventing glucose reabsorption in the kidneys, leading to increased glucose excretion in urine. Clinical trials, such as the EMPA-REG OUTCOME trial, the CANVAS Program, and the DECLARE-TIMI 58 study, have demonstrated their ability to reduce major adverse cardiovascular events, hospitalization for heart failure, and cardiovascular death 1. Additionally, the 2022 AHA/ACC/HFSA guideline for the management of heart failure recommends the use of SGLT2 inhibitors as first-line agents for the treatment of hyperglycemia in patients with diabetes with heart failure or at high risk of heart failure 1. Common side effects include genital mycotic infections and increased urination, while diabetic ketoacidosis and lower limb amputations are rare but serious concerns. SGLT2 inhibitors should be used cautiously in patients with compromised renal function, though specific medications in this class have varying approved uses across different GFR ranges.
From the FDA Drug Label
JARDIANCE is a sodium-glucose co-transporter 2 (SGLT2) inhibitor indicated: as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus, 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: As an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus ( 1). To reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease ( 1)
SGLT2 inhibitors reduce cardiovascular risk in patients with type 2 diabetes, specifically those with established cardiovascular disease. The indications for empagliflozin and canagliflozin include reducing the risk of cardiovascular death and major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease 2, 2, 3.
- Key benefits of SGLT2 inhibitors include:
- Reduction in cardiovascular death
- Reduction in major adverse cardiovascular events
- Improvement in glycemic control
- Patient population: Adults with type 2 diabetes and established cardiovascular disease.
From the Research
Role of SGLT2 Inhibitors in Reducing Cardiovascular Risk
- SGLT2 inhibitors have been shown to reduce cardiovascular risk in patients with type 2 diabetes, with benefits including improved glycaemic control, reduced body weight, and decreased blood pressure 4, 5.
- The EMPA-REG OUTCOME trial and the CANVAS Program demonstrated that the SGLT2 inhibitors empagliflozin and canagliflozin reduced the risk of composite cardiovascular events in high-risk individuals with type 2 diabetes 4.
- Empagliflozin also reduced cardiovascular deaths and improved renal outcomes, suggesting a potential class effect of SGLT2 inhibitors in reducing cardiovascular risk 4.
- A systematic review and meta-analysis found that GLP-1 receptor agonists reduced the risk of major adverse cardiovascular events, with consistent effects in those receiving and not receiving SGLT2 inhibitors at baseline 6.
Mechanisms of Action
- SGLT2 inhibitors work by inhibiting the sodium-glucose co-transporter 2 protein in the proximal tubule of human nephrons, regulating glucose reabsorption and providing cardiovascular benefits 7.
- The pleiotropic effects of SGLT2 inhibitors include modulation of inflammation, oxidative stress, cellular energy metabolism, and housekeeping mechanisms, which may underlie their beneficial effects on cardiovascular risk 7.
Clinical Potential
- The clinical potential of SGLT2 inhibitors in reducing cardiovascular risk is significant, with potential implications for future research and clinical practice 8.
- Emerging evidence suggests that SGLT2 inhibitors may have a class effect in reducing cardiovascular risk, although further studies are needed to confirm this and to determine whether long-term cardiovascular benefits can be extrapolated to populations at lower risk of cardiovascular disease 8.