What is the best Glucagon-like peptide (GLP) agonist?

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Last updated: February 27, 2025View editorial policy

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From the Guidelines

The best GLP-1 agonist currently available is semaglutide, due to its superior efficacy and convenient once-weekly dosing, as demonstrated in the most recent and highest quality study 1.

Key Points

  • Semaglutide has been shown to have the greatest glucose-lowering efficacy among GLP-1 receptor agonists, with a significant reduction in weight and improvement in weight-related comorbidities 1.
  • The STEP trials examined the efficacy of semaglutide, with mean weight loss at 68 weeks of 14.9% and 16.0% in the STEP 1 and STEP 3 trials, respectively 1.
  • Semaglutide has also been shown to decrease the risk of cardiovascular events in adults with overweight or obesity without diabetes, with a lower composite incidence of death due to cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke 1.
  • Other effective options include dulaglutide, liraglutide, and exenatide, but semaglutide is the most effective and convenient option, with a once-weekly dosing regimen 1.

Treatment Considerations

  • Semaglutide typically starts at 0.25mg weekly for the first month, then increases to 0.5mg weekly for another month, with potential further increases to 1.0mg or 2.0mg weekly depending on clinical response and indication.
  • For patients concerned about injections, oral semaglutide is available but requires strict administration guidelines.
  • The "best" agent ultimately depends on individual factors, including insurance coverage, injection preference, side effect tolerance, and specific treatment goals for weight loss or diabetes management.

From the FDA Drug Label

TRULICITY® is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated OZEMPIC is a glucagon-like peptide 1 (GLP-1) receptor agonist indicated

The FDA drug label does not answer the question.

From the Research

GLP-1 Receptor Agonists

  • GLP-1 receptor agonists are effective agents for achieving glycemic control and facilitating weight loss 2, 3
  • They have cardioprotective effects, with some agents reducing the risk of major adverse cardiac events (MACE) 4

Comparison of GLP-1 Receptor Agonists

  • Liraglutide seems to be the most effective GLP-1 receptor agonist in terms of HbA(1c) reduction and weight loss 5
  • Semaglutide has been shown to be effective in helping patients achieve glycemic control and reducing body weight, with a favorable cardiovascular safety profile 2, 3
  • Exenatide twice-daily may offer an advantage where postprandial glucose control is a primary concern, while exenatide extended release once weekly generally outperforms exenatide twice-daily 5

Oral Semaglutide

  • Oral semaglutide is the first oral formulation of a GLP-1 receptor agonist to be approved in the USA 2, 3
  • It has been shown to be effective in helping patients achieve glycemic control and reducing body weight, with a favorable cardiovascular safety profile 2, 3
  • The oral formulation of semaglutide was studied in the PIONEER trials, demonstrating similar efficacy to the presently available GLP-1 receptor agonists with regard to HbA1c lowering and weight loss 2

Cardiovascular Outcome Trials

  • Major cardiovascular outcome trials with GLP-1 receptor agonists have demonstrated their cardiovascular safety and potential cardioprotective effect 4
  • Liraglutide, semaglutide, and albiglutide have been demonstrated to reduce the risk of MACE, whereas lixisenatide and extended-release exenatide had a neutral effect 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

GLP-1 receptor agonists and cardiovascular outcome trials: An update.

Hellenic journal of cardiology : HJC = Hellenike kardiologike epitheorese, 2019

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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