What are the findings of the recently released major study on Glucagon-like peptide-1 (GLP-1) receptor agonists?

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Last updated: February 8, 2025View editorial policy

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From the Guidelines

GLP-1 receptor agonists have been shown to reduce the risk of major adverse cardiovascular events in people with type 2 diabetes. The LEADER trial, a randomized, double-blind trial, assessed the effect of liraglutide, a GLP-1 receptor agonist, versus placebo on cardiovascular outcomes in 9,340 people with type 2 diabetes at high risk for cardiovascular disease or with cardiovascular disease, and found that the primary composite outcome of MI, stroke, or cardiovascular death occurred in fewer participants in the treatment group (13.0%) than in the placebo group (14.9%) [HR 0.87 (95% CI 0.78–0.97); P < 0.001 for noninferiority; P = 0.01 for superiority] 1.

Key Findings

  • Reduced risk of major adverse cardiovascular events: GLP-1 receptor agonists, such as liraglutide, semaglutide, and dulaglutide, have been shown to reduce the risk of major adverse cardiovascular events, including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke, in people with type 2 diabetes 1.
  • Comparable efficacy to SGLT2 inhibitors: Meta-analyses suggest that GLP-1 receptor agonists and SGLT2 inhibitors reduce the risk of atherosclerotic major adverse cardiovascular events to a comparable degree in people with type 2 diabetes and established ASCVD 1.
  • Common adverse effects: Nausea, vomiting, and diarrhea are the most frequently reported adverse effects of GLP-1 receptor agonists, which are dose-dependent and more frequent with short-acting drugs 1.

Implications for Clinical Practice

  • Use in patients with high cardiovascular risk: GLP-1 receptor agonists are recommended for use in patients with type 2 diabetes and high cardiovascular risk, as they have been shown to reduce the risk of major adverse cardiovascular events 1.
  • Monitoring for adverse effects: Patients taking GLP-1 receptor agonists should be monitored for common adverse effects, such as nausea, vomiting, and diarrhea, and dose adjustments should be made as needed 1.

From the Research

Findings of GLP-1 Receptor Agonists Studies

The recently released major studies on Glucagon-like peptide-1 (GLP-1) receptor agonists have shown promising results in terms of cardiovascular safety and efficacy. The key findings are:

  • GLP-1 receptor agonists have been shown to reduce the risk of major adverse cardiovascular events, cardiovascular mortality, and all-cause mortality in patients with type 2 diabetes 2, 3, 4.
  • These medications have also been found to have a favorable risk-benefit balance, allowing for individualized treatment choices for patients 2.
  • The studies have consistently demonstrated that GLP-1 receptor agonists can reduce the risk of death from cardiovascular causes and fatal or non-fatal stroke compared to placebo 3, 4.
  • Additionally, GLP-1 receptor agonists have been associated with a lower risk of cardiovascular complications, including ischemic heart disease, heart failure, arrhythmias, hypertension, stroke, and atrial fibrillation 5.

Cardiovascular Benefits

The cardiovascular benefits of GLP-1 receptor agonists are well-documented and include:

  • Reduced risk of major adverse cardiovascular events (MACE) 2, 3, 4
  • Lower risk of cardiovascular mortality and all-cause mortality 2, 3, 4
  • Reduced risk of non-fatal myocardial infarction and non-fatal stroke 3, 4
  • Protective effects on cardiovascular health, renal outcomes, and adverse events in individuals with obesity and without type 2 diabetes 5

Safety and Efficacy

The safety and efficacy of GLP-1 receptor agonists have been evaluated in several studies, with findings including:

  • GLP-1 receptor agonists are associated with a significantly lower risk of all-cause mortality and several cardiovascular complications 5
  • These medications have a favorable risk-benefit balance, with benefits extending to patients with existing cardiovascular risk factors 4
  • However, more evidence is required to determine if these benefits extend to patients without cardiovascular risk factors 4

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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