From the Guidelines
GLP-1 receptor agonists are synthetic medications designed to mimic the action of the naturally occurring hormone glucagon-like peptide-1 (GLP-1), but they are not natural mimickers. While they work by activating the same receptors as the body's natural GLP-1, these medications have been modified to resist degradation by enzymes, allowing them to remain active in the body much longer than natural GLP-1 1. Examples include semaglutide (Ozempic, Wegovy, Rybelsus) and liraglutide (Victoza, Saxenda), which have been shown to be effective in weight loss and improving weight-related comorbidities 1. These medications work by stimulating insulin secretion when blood glucose is high, suppressing glucagon release, slowing gastric emptying, and reducing appetite through central nervous system effects. This combination of actions helps control blood sugar and often leads to weight loss, making these medications valuable for treating type 2 diabetes and obesity.
Some key points to consider when using GLP-1 receptor agonists include:
- They have been shown to reduce the risk of cardiovascular events in adults with overweight or obesity without diabetes 1
- They can be used in combination with other medications, such as metformin, sulfonylureas, and thiazolidinediones, to achieve better glycemic control 1
- They have a minimal risk of hypoglycemia, but may increase the hypoglycemic potential of insulin and sulfonylureas when combined with those medications 1
- They can be considered in patients with type 2 diabetes without established cardiovascular disease but with the presence of specific indicators of high risk 1
Overall, GLP-1 receptor agonists are a valuable treatment option for type 2 diabetes and obesity, and their use should be considered in patients who are at high risk of cardiovascular events or who have not achieved adequate glycemic control with other medications.
From the FDA Drug Label
Liraglutide is an acylated human Glucagon-Like Peptide-1 (GLP-1) receptor agonist with 97% amino acid sequence homology to endogenous human GLP-1(7-37). GLP-1(7-37) represents <20% of total circulating endogenous GLP-1 Like GLP-1(7-37), liraglutide activates the GLP-1 receptor, a membrane-bound cell-surface receptor coupled to adenylyl cyclase by the stimulatory G-protein, Gs, in pancreatic beta cells.
GLP-1 receptor agonists are designed to mimic the action of the naturally occurring hormone GLP-1.
- They have a similar amino acid sequence to endogenous human GLP-1(7-37).
- They activate the GLP-1 receptor, leading to increased insulin secretion and decreased glucagon secretion in a glucose-dependent manner.
- Examples of GLP-1 receptor agonists include liraglutide and semaglutide. Therefore, GLP-1 receptor agonists can be considered natural mimickers of the GLP-1 hormone 2.
From the Research
GLP-1 Receptor Agonists as Natural Mimickers
- GLP-1 receptor agonists are a class of medications that mimic the action of the naturally occurring hormone glucagon-like peptide-1 (GLP-1) 3, 4.
- GLP-1 is an incretin peptide hormone released from the lower digestive tract that stimulates insulin secretion, suppresses glucagon secretion, and decreases hunger 4.
- GLP-1 receptor agonists work by improving glucose-dependent insulin release, suppressing glucagon release, suppressing hepatic glucose output, and decreasing the rate of gastric emptying, thereby reducing appetite 3.
Mechanism of Action
- The mechanism of action of GLP-1 receptor agonists is similar to that of natural GLP-1, which is partly responsible for insulin release and for attenuating hyperglycemia during meals (ie, the incretin effect) 3.
- GLP-1 receptor agonists exert their effects by binding to GLP-1 receptors, which are found in various tissues, including the pancreas, liver, and brain 5.
Examples of GLP-1 Receptor Agonists
- There are several GLP-1 receptor agonists available, including exenatide, liraglutide, albiglutide, dulaglutide, lixisenatide, and semaglutide 3, 5.
- Oral semaglutide is a newer formulation that has shown promising results in clinical trials, with efficacy in glycemic management and body weight loss, and a low risk of hypoglycemia 4, 6.
Benefits and Risks
- GLP-1 receptor agonists have been shown to have several benefits, including improved glycemic control, weight loss, and reduced risk of major adverse cardiovascular events (MACE) 7, 6.
- However, they can also have adverse effects, such as gastrointestinal symptoms, hypotension, syncope, and increased risk of pancreatitis 7.