What are the benefits of Glucagon-like peptide-1 (GLP-1)?

From the Guidelines

GLP-1 receptor agonists offer significant benefits for patients with type 2 diabetes and obesity, including improved glycemic control, weight loss, and cardiovascular protection, as demonstrated by the LEADER trial 1 and SUSTAIN 6 trial 1. The benefits of GLP-1 receptor agonists can be summarized as follows:

• Improved glycemic control by stimulating insulin release and reducing glucagon production
• Significant weight loss by decreasing appetite and slowing stomach emptying, with patients typically losing 5-15% of their body weight depending on the specific medication
• Cardiovascular protection by reducing heart attack and stroke risk, particularly in patients with established heart disease, as shown by the LEADER trial which reported a 13% reduction in major adverse cardiovascular events 1
• Additional benefits include improved blood pressure, reduced inflammation, and potential kidney protection
• Side effects are generally manageable and include nausea, vomiting, and diarrhea that often improve over time, as outlined in Table 2 of the study by 1

The use of GLP-1 receptor agonists has been supported by recent studies, including the LEADER trial 1 and the SUSTAIN 6 trial 1, which demonstrated a significant reduction in major adverse cardiovascular events. Additionally, a recent randomised double-blind study found that semaglutide 2.4 mg weekly reduced the primary cardiovascular endpoint of death from cardiovascular causes, non-fatal myocardial infarction or non-fatal stroke by 21% compared to placebo 1. It is essential to consider the individual patient profile, procedure, and anaesthetic technique when using GLP-1 receptor agonists in the peri-operative setting, as highlighted by the consensus statement from the Association of Anaesthetists 1. Overall, the benefits of GLP-1 receptor agonists make them an effective tool for managing type 2 diabetes and obesity, and their use should be considered in patients with established heart disease or at high risk of cardiovascular events.

From the FDA Drug Label

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 BYETTA 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 benefits of GLP-1 include:

• Enhanced glucose-dependent insulin secretion: GLP-1 receptor agonists, such as semaglutide and exenatide, increase insulin secretion from the pancreatic beta cells in response to high glucose levels.
• Suppression of inappropriately elevated glucagon secretion: GLP-1 receptor agonists reduce glucagon secretion, leading to decreased hepatic glucose output and decreased insulin demand.
• Slowing of gastric emptying: GLP-1 receptor agonists delay the movement of food from the stomach to the small intestine, reducing the rate at which glucose enters the bloodstream.
• Reduced food intake: Administration of GLP-1 receptor agonists has been shown to decrease food intake in both animals and humans.
• Improved glycemic control: GLP-1 receptor agonists reduce fasting and postprandial glucose concentrations in patients with type 2 diabetes 2, 3, 3.

From the Research

Benefits of GLP-1

• The benefits of GLP-1 receptor agonists (GLP-1 RAs) include augmentation of hyperglycemia-induced insulin secretion, suppression of glucagon secretion, deceleration of gastric emptying, and reduction in calorie intake and body weight 4.
• GLP-1 RAs have been shown to be effective in reducing HbA1c levels, with some agents having a more profound effect on overnight and fasting plasma glucose 4, 5.
• In addition to their glucose-lowering effects, GLP-1 RAs have also been shown to have beneficial effects on weight loss and cardiovascular risk markers 5, 6.
• GLP-1 RAs have been demonstrated to reduce the risk of cardiovascular events, such as acute myocardial infarction or stroke, and associated mortality 4, 7.
• The use of GLP-1 RAs may also help prevent renal complications of type 2 diabetes 4.

Mechanisms of Action

• GLP-1 RAs work by improving glucose-dependent insulin release, suppressing glucagon release, suppressing hepatic glucose output, and decreasing the rate of gastric emptying 8.
• The different mechanisms of action of GLP-1 RAs result in generally greater efficacy, albeit at the expense of slightly increased gastrointestinal symptoms 8.

Clinical Use

• GLP-1 RAs are recommended as a preferred add-on agent to existing metformin monotherapy, as first-line therapy if metformin is contraindicated or poorly tolerated, and for use in combination with other oral glucose-lowering agents or basal insulin 5.
• The choice of a specific GLP-1 RA will depend on patient preferences, potential adverse effects, and cost 8.
• GLP-1 RAs have a favorable safety profile, with the most common adverse effect being gastrointestinal upset, which typically wanes during the early weeks of therapy 7.