Which Glucagon-Like Peptide-1 (GLP1) receptor agonist?

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Last updated: February 20, 2025View editorial policy

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From the Guidelines

Semaglutide is the recommended Glucagon-Like Peptide-1 (GLP1) receptor agonist due to its superior efficacy in reducing cardiovascular events and its convenient once-weekly dosing regimen. This recommendation is based on the results of the SUSTAIN-6 trial, which demonstrated a significant reduction in major adverse cardiovascular events with semaglutide compared to placebo 1. The trial showed that semaglutide reduced the risk of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke by 26% compared to placebo.

Key Benefits of Semaglutide

  • Once-weekly dosing, which improves adherence
  • Superior efficacy in reducing cardiovascular events
  • Significant weight loss and improved glycemic control

Alternative Options

For patients who cannot use or access semaglutide, alternative GLP-1 receptor agonists include:

  • Liraglutide (Victoza): 0.6 mg daily, increased to 1.2 mg after a week, then 1.8 mg if needed
  • Dulaglutide (Trulicity): 0.75 mg weekly, can be increased to 1.5 mg
  • Exenatide (Byetta): 5 mcg twice daily for one month, then 10 mcg twice daily

Important Considerations

When starting any GLP-1 agonist, monitor for gastrointestinal side effects like nausea and vomiting, which usually improve over time 1. Advise patients to stay well-hydrated and eat smaller, more frequent meals to minimize these effects. The choice of GLP-1 receptor agonist should be individualized based on patient-specific factors, such as comorbidities, medication adherence, and potential side effects.

From the FDA Drug Label

OZEMPIC is a glucagon-like peptide 1 (GLP-1) receptor agonist indicated as: • an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (1). • to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease (1)

The GLP-1 receptor agonist is semaglutide (SQ), also known as OZEMPIC 2.

  • Key points:
    • Indicated for improving glycemic control in adults with type 2 diabetes mellitus
    • Indicated to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease
    • Administered via subcutaneous injection
    • Available in single-patient-use pens with doses of 0.25 mg, 0.5 mg, or 1 mg per injection

From the Research

Glucagon-Like Peptide-1 (GLP1) Receptor Agonist

  • Semaglutide is a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) indicated for glycaemic management in adults with type 2 diabetes (T2D) 3, 4, 5, 6, 7
  • Oral semaglutide administration can help decrease glycated haemoglobin (HbA1c) and body weight in people with uncontrolled T2D 3, 4, 5
  • Semaglutide has been compared head-to-head with other GLP-1RAs, such as liraglutide and dulaglutide, and has been found to provide significant and clinically relevant reductions in HbA1c, fasting plasma glucose (FPG), glucose excursions, body weight and blood pressure 3, 4, 5, 7

Efficacy and Safety

  • Oral semaglutide was non-inferior to subcutaneous semaglutide and superior to placebo and other GLP-1 RA comparators in reducing HbA1c and body weight 3
  • Oral semaglutide was associated with low proportions of patients experiencing severe or blood glucose-confirmed symptomatic hypoglycemia when added to oral glucose-lowering therapies, and did not increase the incidence of such events when added to insulin 4
  • The tolerability profile of oral semaglutide was consistent with that seen for injectable GLP-1RAs, with gastrointestinal side effects seen most frequently 3, 4, 5, 7

Administration and Dosage

  • Oral semaglutide should be taken on an empty stomach upon waking with a sip (≤120 mL) of plain water and at least 30 minutes before the first food, beverage, or other oral medications of the day 6
  • The most common adverse effects of oral semaglutide are gastrointestinal (typically nausea, diarrhea, and vomiting) 3, 4, 5, 6, 7

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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