Glucagon-like peptide-1 receptor agonists, or GLP-1s, are medications that imitate a hormone naturally produced in the gut called GLP-1, which is released after a meal. These drugs have gained public attention for their effects on metabolic health. Initially developed for managing type 2 diabetes, their use has since expanded, leading to wider recognition.
The Mechanism of Action
GLP-1 receptor agonists influence several bodily systems involved in metabolism and appetite. When administered, these drugs bind to and activate GLP-1 receptors found on cells in the pancreas, brain, and other tissues. This activation triggers effects that help regulate blood sugar and reduce energy intake by mimicking the body’s natural incretin system.
One of the primary actions occurs in the pancreas. In response to glucose from a meal, GLP-1 agonists stimulate pancreatic beta-cells to release insulin, which helps the body’s cells absorb sugar from the bloodstream. The drugs also inhibit the release of glucagon, a hormone that tells the liver to produce more sugar. This combination helps control blood glucose.
Another effect is the slowing of gastric emptying, the rate at which food leaves the stomach. This action prolongs the feeling of fullness after eating, which means sugar from meals is absorbed more slowly. This contributes to better blood sugar control and a reduction in overall calorie consumption.
These drugs also have a direct impact on the central nervous system to regulate appetite. GLP-1 agonists cross the blood-brain barrier and activate receptors in brain areas that control hunger, such as the hypothalamus. This action enhances feelings of satiety and can diminish food cravings.
Approved Medical Uses
Type 2 Diabetes
GLP-1 receptor agonists were first developed and approved for the treatment of type 2 diabetes. They are often recommended when initial therapies like metformin are not sufficient or tolerated. Because they help manage blood sugar, common brand names prescribed for diabetes include Ozempic, Victoza, and Trulicity.
The American Diabetes Association’s standards of care recommend GLP-1 agonists as a first-line therapy for certain patients with type 2 diabetes. This is particularly true for those who also have established atherosclerotic cardiovascular disease or obesity. Their ability to improve glucose control while offering weight and cardiovascular benefits makes them a valuable treatment option.
Chronic Weight Management
The weight loss observed in patients taking GLP-1s for diabetes led to their development for chronic weight management. For this purpose, drugs like Wegovy and Saxenda are prescribed at specific doses. These medications are intended for individuals with obesity or those who are overweight and have related health conditions.
A newer evolution in this class includes dual-agonist medications. Mounjaro and Zepbound, for example, act on both GLP-1 and another incretin hormone receptor called GIP. This dual action has been shown to produce even more significant weight loss and improvements in metabolic health.
Common Side Effects and Health Considerations
The most frequently reported side effects of GLP-1 receptor agonists are gastrointestinal. Users commonly experience nausea, vomiting, diarrhea, and constipation, especially when first starting the medication or increasing the dose. These symptoms may subside as the body adjusts. To manage these effects, providers typically start patients on a low dose and increase it gradually.
Beyond gastrointestinal issues, there are more serious, though less common, health risks. The U.S. Food and Drug Administration (FDA) requires a boxed warning on these medications for a risk of thyroid C-cell tumors. This warning is based on rodent studies, and it is not known if this risk translates to humans. Other potential risks include pancreatitis (inflammation of the pancreas) and gallbladder problems like gallstones.
A consideration for long-term use is the potential for weight regain after stopping the medication. The effects of GLP-1 agonists on appetite and weight are only present while the drug is being taken. Once discontinued, the body’s previous appetite signals can return, often leading to a reversal of the weight loss. This highlights that these medications are a long-term treatment.
Due to delayed gastric emptying, there is a potential risk of aspiration during medical procedures that require anesthesia. In 2023, the American Society of Anesthesiologists issued guidance suggesting that patients hold their GLP-1 medication before a planned surgery. This precaution is intended to ensure the stomach is empty, reducing the risk of complications.
Administration and Different Formulations
The most common method for taking GLP-1 receptor agonists is a self-administered subcutaneous injection. These medications are provided in pre-filled pen devices that are easy for patients to use. Depending on the specific drug, injections are administered on a daily or weekly schedule. Common injection sites include the abdomen, thigh, or upper arm.
While injections are standard, an oral formulation is also available as an alternative. Rybelsus is a brand of semaglutide that comes in a tablet form. It is taken once daily on an empty stomach with a small amount of water, at least 30 minutes before consuming any other food, drink, or medications to ensure proper absorption.