What is the comparison between Glucagon-like peptide-1 (GLP-1) and Sodium-glucose cotransporter 2 (SGLT2) inhibitors?

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Last updated: April 12, 2025View editorial policy

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From the Guidelines

GLP-1 receptor agonists and SGLT2 inhibitors are both effective in reducing major adverse cardiovascular events (MACE) and improving quality of life (QOL) in patients with type 2 diabetes, but the choice between them should be based on individual patient characteristics and needs, with SGLT2 inhibitors being preferred for patients with heart failure or chronic kidney disease, and GLP-1 receptor agonists being preferred for patients needing significant weight loss or with established cardiovascular disease, as recommended by the most recent guideline from the American College of Cardiology (1).

Key Differences Between GLP-1 and SGLT2 Inhibitors

  • GLP-1 receptor agonists work by mimicking incretin hormones, increasing insulin secretion, reducing glucagon, slowing gastric emptying, and promoting satiety, resulting in significant weight loss (5-15%) and A1C reduction (1-2%) (1)
  • SGLT2 inhibitors block glucose reabsorption in the kidneys, causing glucose excretion in urine, leading to modest weight loss (2-4%) and A1C reduction (0.5-1%) (1)

Patient Characteristics and Preferences

  • Patients with heart failure or chronic kidney disease may benefit more from SGLT2 inhibitors, which have been shown to reduce hospitalizations for heart failure and progression of chronic kidney disease (1)
  • Patients needing significant weight loss or with established cardiovascular disease may benefit more from GLP-1 receptor agonists, which have been shown to result in significant weight loss and reduction in MACE (1)

Combination Therapy

  • Many patients may benefit from combination therapy targeting multiple pathways simultaneously, with both GLP-1 receptor agonists and SGLT2 inhibitors being used together to achieve optimal glycemic control and reduce cardiovascular risk (1)

From the Research

Comparison of GLP-1 and SGLT2 Inhibitors

  • GLP-1 receptor agonists and SGLT2 inhibitors are both used to treat type 2 diabetes, with additional benefits of weight loss and blood pressure reduction 2, 3.
  • Both classes of drugs have been shown to reduce the risk of major cardiovascular events, with a similar magnitude of benefit ranging from 12 to 14% reduction of risk 4.
  • However, SGLT2 inhibitors have been found to have a greater benefit in reducing hospitalization for heart failure, with a threefold greater benefit compared to GLP-1 receptor agonists 4.
  • GLP-1 receptor agonists may be more effective in reducing the risk of stroke, and have been found to have a significant benefit in reducing hospitalization for heart failure, although to a lesser extent than SGLT2 inhibitors 4.
  • The choice between GLP-1 receptor agonists and SGLT2 inhibitors should be based on individual patient profiles and specificities of each molecule, taking into account factors such as cardiovascular risk, kidney function, and history of heart failure or other comorbidities 5, 3, 6.

Cardiovascular Benefits

  • Both GLP-1 receptor agonists and SGLT2 inhibitors have been shown to reduce the risk of major cardiovascular events, including myocardial infarction, stroke, and cardiovascular mortality 2, 5, 4.
  • SGLT2 inhibitors have been found to have a greater benefit in reducing hospitalization for heart failure, particularly in patients with established heart failure or at high risk of heart failure 3, 4.
  • GLP-1 receptor agonists may be more effective in reducing the risk of stroke, although the evidence is not as strong as for SGLT2 inhibitors 4.

Renal Benefits

  • Both GLP-1 receptor agonists and SGLT2 inhibitors have been found to have renoprotective effects, although the evidence is not as strong as for cardiovascular benefits 2, 3.
  • SGLT2 inhibitors may have a greater benefit in reducing the risk of end-stage kidney disease or kidney failure, although more research is needed to confirm this 3.
  • GLP-1 receptor agonists may also have a benefit in reducing kidney damage, although the evidence is not as strong as for SGLT2 inhibitors 2.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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