From the Guidelines
The cardioprotective effects of SGLT2 inhibitors and GLP-1 receptor agonists are due to their ability to reduce major adverse cardiovascular events, heart failure, and cardiovascular mortality through distinct but complementary mechanisms, as demonstrated in recent clinical trials 1. The mechanisms of action of SGLT2 inhibitors, such as empagliflozin, dapagliflozin, and canagliflozin, primarily involve promoting glucose excretion in urine, reducing blood pressure, decreasing cardiac preload and afterload, and improving cardiac energetics through ketone body production, as well as reducing inflammation, oxidative stress, and fibrosis in cardiac tissue 1. GLP-1 receptor agonists, such as semaglutide, liraglutide, and dulaglutide, provide cardioprotection by improving endothelial function, reducing inflammation, decreasing blood pressure, promoting weight loss, and improving lipid profiles 1. Key benefits of these medications include:
- Reduction in major adverse cardiovascular events, such as myocardial infarction, stroke, and cardiovascular death
- Reduction in heart failure hospitalization and cardiovascular mortality
- Improvement in endothelial function, reduction in inflammation, and improvement in lipid profiles
- Ability to work through multiple pathways beyond simple glucose control, explaining their cardiovascular benefits even in patients without diabetes Recent clinical trials, such as the EMPA-REG OUTCOME trial, CANVAS Program, and DECLARE-TIMI 58 study, have demonstrated the efficacy of SGLT2 inhibitors in reducing cardiovascular events and mortality 1. Similarly, trials such as the LEADER trial and others have shown the benefits of GLP-1 receptor agonists in reducing major adverse cardiovascular events 1. Therefore, SGLT2 inhibitors and GLP-1 receptor agonists are recommended for patients with type 2 diabetes and established cardiovascular disease or multiple risk factors for cardiovascular disease, as they have been shown to reduce the risk of major adverse cardiovascular events and improve cardiovascular outcomes 1.
From the FDA Drug Label
To reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease. To reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease. 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.
The cardioprotective effect of SGLT2 inhibitors, such as empagliflozin 2 and canagliflozin 3, is due to their ability to:
- Reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease.
- Reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease.
- 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. However, the cardioprotective effect of GLP-1 inhibitors is not mentioned in the provided drug labels.
From the Research
Cardioprotective Effects of SGLT2 and GLP-1 Inhibitors
The cardioprotective effects of SGLT2 (Sodium-Glucose Linked Transporter 2) and GLP-1 (Glucagon-Like Peptide-1) inhibitors are well-documented in various studies 4, 5, 6, 7, 8. These effects include:
- Reduction in cardiovascular and all-cause mortality
- Decreased risk of chronic kidney disease progression
- Decrease in hospitalization for heart failure (HF)
- Stroke prevention
Mechanisms of Cardioprotection
Several mechanisms have been suggested to contribute to the cardioprotective effects of SGLT2 inhibitors, including:
- Increase in natriuresis and diuretic effects, leading to a reduction in preload and myocardial stretch 6
- Decrease in blood pressure and afterload 6
- Favorable effects on cardiac metabolism, including increased production of ketones 6, 8
- Anti-inflammatory and antifibrotic effects 6, 8
- Influence on ion homeostasis and oxidative stress markers 8
Combination Therapy
The combination of SGLT2 inhibitors and GLP-1 receptor agonists has been shown to have additive effects on lowering HbA1c level, systolic blood pressure, and body weight, as well as reducing major cardiovascular events and renal decompensation 5, 7. This combination therapy may be beneficial for patients with type 2 diabetes and cardiovascular disease.
Clinical Implications
The cardioprotective effects of SGLT2 and GLP-1 inhibitors have important clinical implications, including: