What is the effect of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist?

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From the Guidelines

GLP-1 Receptor Agonists are a class of medications that have a positive effect on patients with type 2 diabetes and obesity by lowering fasting plasma glucose and glycated haemoglobin, promoting weight loss, and reducing the risk of cardiovascular events 1.

Key Benefits

  • Lower risk of hypoglycaemia: GLP-1 Receptor Agonists have a low risk of hypoglycaemia with no clinically significant difference in hypoglycaemic events among drugs within the class 1.
  • Weight loss: These medications promote weight loss by delaying gastric emptying and increasing satiety, in patients with and without diabetes mellitus 1.
  • Cardiovascular benefits: GLP-1 Receptor Agonists have been shown to reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes 1.

Recommended GLP-1 RAs

  • Exenatide (Byetta, Bydureon) 5-10 mcg twice daily or 2 mg weekly
  • Liraglutide (Victoza, Saxenda) 1.2-1.8 mg daily
  • Dulaglutide (Trulicity) 0.75-1.5 mg weekly
  • Semaglutide (Ozempic, Wegovy) 0.5-1 mg weekly

Important Considerations

  • These medications should be initiated and monitored by a healthcare professional, with dose adjustments as needed to minimize side effects and optimize glucose control 1.
  • Treatment duration is typically long-term, with regular assessments of efficacy, safety, and potential dose adjustments.
  • It is essential to follow the prescribed treatment plan and attend regular follow-up appointments to ensure safe and effective use of GLP-1 RAs.

Side Effects

  • Nausea, vomiting, and diarrhea are the most common side effects of GLP-1 Receptor Agonists, but usually are tolerable with dose titration and abate over several weeks to months 1.

From the FDA Drug Label

  1. 1 Mechanism of Action Incretins, such as glucagon-like peptide-1 (GLP-1), enhance glucose-dependent insulin secretion and exhibit other antihyperglycemic actions following their release into the circulation from the gut Exenatide is a GLP-1 receptor agonist that enhances glucose-dependent insulin secretion by the pancreatic beta-cell, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying.

The effect of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist is to:

  • Enhance glucose-dependent insulin secretion by the pancreatic beta-cell
  • Suppress inappropriately elevated glucagon secretion
  • Slow gastric emptying This leads to an improvement in glycemic control by reducing fasting and postprandial glucose concentrations in patients with type 2 diabetes. 2

From the Research

Effects of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist

The effects of GLP-1 receptor agonists are numerous and well-documented in various studies 3, 4, 5, 6, 7. Some of the key effects include:

  • Lowering A1C and weight while having a low risk of hypoglycemia 3, 7
  • Documented cardiovascular benefits, including reducing the risk of severe adverse cardiovascular events 4, 5
  • Promoting weight loss and improving kidney function in people living with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) 4, 5
  • Reducing the frequency of major cardiovascular events and improving renal outcomes 5, 6
  • Having a low risk of hypoglycemia and promoting a sense of fullness via brain pathways 4, 6

Mechanism of Action

The mechanism of action of GLP-1 receptor agonists involves:

  • Stimulating insulin secretion in response to glucose levels 4, 6
  • Inhibiting glucagon release 4, 6
  • Delaying stomach emptying and generating a sense of fullness via brain pathways 4, 6
  • Having pleiotropic effects on T2D pathophysiology, including improving glycaemia, reducing body weight, and having cardio- and renal protective potentials 6

Clinical Use

GLP-1 receptor agonists are widely used in the treatment of type 2 diabetes, particularly in overweight patients and those with cardiovascular disease 3, 4, 5, 6. They are also used in patients with T2DM and CKD, where they have been shown to have renoprotective properties 5. The choice of GLP-1 receptor agonist depends on various factors, including efficacy, safety, and patient preferences 3, 7.

Safety and Efficacy

The safety and efficacy of GLP-1 receptor agonists have been evaluated in numerous clinical trials 3, 4, 5, 6, 7. Common side effects include gastrointestinal toxicity, which can be mitigated by gradually increasing the dose 4. Head-to-head clinical studies have demonstrated that all GLP-1 receptor agonists are effective therapeutic options at reducing A1C, although differences exist in terms of magnitude of effect on A1C and weight as well as frequency of adverse effects 3, 7.

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

3
Research

GLP-1 receptor agonists: an updated review of head-to-head clinical studies.

Therapeutic advances in endocrinology and metabolism, 2021

6
Research

How glucagon-like peptide 1 receptor agonists work.

Endocrine connections, 2021

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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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