What is the best SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitor or GLP-1 (Glucagon-Like Peptide-1) receptor agonist for cardiac protection?

From the Guidelines

For cardiac protection, the best SGLT2 inhibitor is empagliflozin (Jardiance) at 10-25mg daily, while the best GLP-1 receptor agonist is semaglutide (Ozempic/Wegovy) at 0.5-1mg weekly injection or 14mg oral daily (Rybelsus). The choice between these two classes of medications depends on individual patient factors, including the presence of established cardiovascular disease, kidney disease, and other comorbidities. According to the most recent guidelines 1, in people with type 2 diabetes and established ASCVD, multiple ASCVD risk factors, or chronic kidney disease (CKD), an SGLT2 inhibitor with demonstrated cardiovascular benefit is recommended to reduce the risk of major adverse cardiovascular events and/or heart failure hospitalization. Some key points to consider when selecting an SGLT2 inhibitor or GLP-1 receptor agonist for cardiac protection include:

• The patient's individual cardiovascular risk profile, including the presence of established ASCVD, kidney disease, and other comorbidities
• The potential benefits and risks of each medication, including the risk of genital infections with SGLT2 inhibitors and gastrointestinal symptoms with GLP-1 agonists
• The patient's ability to tolerate the medication and adhere to the prescribed treatment regimen As noted in the 2025 guidelines 1, combined therapy with an SGLT2 inhibitor with demonstrated cardiovascular benefit and a GLP-1 RA with demonstrated cardiovascular benefit may be considered for additive reduction of the risk of adverse cardiovascular and kidney events. It's also worth noting that SGLT2 inhibitors like empagliflozin or dapagliflozin (10mg daily) are particularly beneficial for patients with heart failure with reduced ejection fraction, regardless of diabetes status, as demonstrated in studies such as the EMPA-REG OUTCOME trial and the DAPA-HF study 1. Overall, the selection of an SGLT2 inhibitor or GLP-1 receptor agonist for cardiac protection should be individualized based on the patient's unique needs and circumstances, and should be guided by the most recent clinical evidence and guidelines, including those from 2025 1.

From the FDA Drug Label

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 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 WEGOVY is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated in combination with a reduced calorie diet and increased physical activity: to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established cardiovascular disease and either obesity or overweight

The best option for cardiac protection between SGLT2 inhibitors and GLP-1 receptor agonists is not explicitly stated in the provided drug labels. However, based on the available information:

• Canagliflozin (SGLT2 inhibitor) is indicated to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease 2.
• Semaglutide (GLP-1 receptor agonist) is indicated to reduce the risk of major adverse cardiovascular events in adults with established cardiovascular disease and either obesity or overweight 3. It is essential to consider individual patient factors, such as the presence of diabetes, obesity, and established cardiovascular disease, when selecting the most appropriate treatment option for cardiac protection. Key points:
• Both canagliflozin and semaglutide have indications for reducing the risk of major adverse cardiovascular events.
• The choice between these medications should be based on individual patient characteristics and medical history.

From the Research

Cardiac Protection with SGLT2 Inhibitors or GLP-1 Receptor Agonists

The choice between SGLT2 inhibitors and GLP-1 receptor agonists for cardiac protection depends on various factors, including the patient's individual profile and specific disease conditions.

• SGLT2 inhibitors have been shown to reduce the risk of heart failure hospitalizations and cardiovascular mortality in patients with type 2 diabetes and established cardiovascular disease 4, 5.
• GLP-1 receptor agonists have also demonstrated cardiovascular benefits, including a reduced risk of major cardiovascular events and mortality 4, 6.
• A study comparing the two classes of drugs suggested that SGLT2 inhibitors may be more effective in reducing the incidence of heart failure, while GLP-1 receptor agonists may have a greater effect on reducing the risk of stroke 7.

Patient-Specific Considerations

When selecting between SGLT2 inhibitors and GLP-1 receptor agonists, healthcare providers should consider the following factors:

• Patients with heart failure (with reduced ejection fraction) or chronic kidney disease may benefit more from SGLT2 inhibitors 6, 5.
• Patients at high risk of cardiovascular disease or with established cardiovascular disease may benefit more from GLP-1 receptor agonists 6.
• The presence of other comorbidities, such as obesity or pancreatitis, may also influence the choice of therapy 6.

Mechanisms of Action

The mechanisms by which SGLT2 inhibitors and GLP-1 receptor agonists exert their cardiac protective effects are not fully understood but are thought to involve:

• Reduction in glucose levels and improvement in insulin sensitivity 4, 6.
• Decrease in blood pressure and reduction in cardiac workload 6, 5.
• Anti-inflammatory and anti-fibrotic effects 8.
• Improvement in cardiac biomarkers and reduction in heart failure signaling 8.