Glucagon-like peptide-1 (GLP-1) receptor agonists are medications that mimic a hormone the gut releases after eating. Initially developed for type 2 diabetes, these drugs gained attention for their impact on blood sugar and body weight. They work by copying the natural GLP-1 hormone, which helps manage metabolism and appetite.
The Mechanism of GLP-1 Agonists
GLP-1 receptor agonists work by activating receptors in the pancreas and brain. This process initiates physiological responses that influence blood sugar and appetite. The medications are designed to last longer in the body than the natural GLP-1 hormone, which breaks down quickly.
A primary action is to stimulate the pancreas to release insulin when blood glucose is high. Insulin helps cells absorb glucose from the bloodstream, lowering blood sugar levels. This process is glucose-dependent, meaning insulin secretion is prompted by eating, which prevents blood sugar from dropping too low.
Simultaneously, GLP-1 agonists suppress the release of glucagon, a hormone with the opposite effect of insulin. Glucagon signals the liver to release more glucose into the bloodstream. By inhibiting glucagon after meals, these medications prevent an unnecessary rise in blood sugar.
Another part of their function involves slowing gastric emptying, the rate at which food moves from the stomach to the small intestine. This delay slows carbohydrate absorption, leading to a more gradual increase in blood sugar. This effect also contributes to a prolonged feeling of fullness.
These medications also act on the central nervous system. GLP-1 receptors are found in brain areas that regulate appetite, such as the hypothalamus. Activating these receptors increases feelings of satiety and reduces hunger signals, leading to lower calorie consumption.
Approved Medical Uses
The U.S. Food and Drug Administration (FDA) has approved GLP-1 receptor agonists for managing type 2 diabetes and for chronic weight management. For type 2 diabetes, they are often prescribed when other drugs like metformin are not sufficient. Brand names for diabetes management include Ozempic (semaglutide), Trulicity (dulaglutide), and Victoza (liraglutide).
For weight management, specific dosages are approved for adults with obesity or who are overweight with a related health issue like high blood pressure. Wegovy, which contains a higher dose of semaglutide than Ozempic, is approved for this purpose. Liraglutide is also available in a higher dose for weight management under a different brand name.
A newer development is dual-agonist medications that target more than one receptor. Tirzepatide, known as Mounjaro for diabetes and Zepbound for weight management, activates both GLP-1 and GIP receptors. The combination of activating both has been shown to produce more significant reductions in blood sugar and body weight.
The specific formulation and dosage dictate the approved use, even when the active ingredient is the same across different products.
Common Side Effects and Health Considerations
The most frequently reported side effects of GLP-1 receptor agonists are gastrointestinal. Patients may experience nausea, vomiting, diarrhea, or abdominal pain, particularly when starting the medication or after a dose increase. These symptoms are often mild and tend to decrease as the body adjusts.
Beyond common digestive issues, there are less frequent but more serious health considerations. Prescribing information includes warnings about a potential risk of pancreatitis (inflammation of the pancreas) and gallbladder problems. Patients are advised to report any severe abdominal pain to their healthcare provider.
A significant warning involves a potential risk of thyroid C-cell tumors, based on studies in rodents. While it is not known if this risk translates to humans, the FDA requires a boxed warning on the labels. These drugs are not recommended for patients with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
Dehydration can also occur from persistent vomiting or diarrhea, which could lead to kidney issues. For individuals with type 2 diabetes, there is a possibility of low blood sugar (hypoglycemia), especially when used with other diabetes drugs. It is important for patients to discuss their full medical history with their healthcare provider.
Administration and Long-Term Use
GLP-1 receptor agonists are most commonly administered as a subcutaneous injection into the fatty tissue under the skin. The frequency varies by drug. Some, like Victoza, require daily administration, while others like Ozempic, Wegovy, and Mounjaro are injected once a week.
An oral formulation of semaglutide, branded as Rybelsus, is available for treating type 2 diabetes. This daily pill is an alternative for those who prefer not to use injections. It must be taken on an empty stomach with a small amount of water 30 minutes before the first meal of the day.
These medications are designed for long-term use, as type 2 diabetes and obesity are chronic conditions. The metabolic benefits, such as lower blood sugar and reduced weight, are sustained only as long as the patient takes the drug. If the medication is stopped, blood sugar levels often rise, and much of the lost weight is regained.
For this reason, these drugs are a long-term management tool. They are most effective when integrated into a comprehensive lifestyle plan that includes consistent dietary changes and regular physical activity. This combined approach helps maximize the medication’s effects and supports overall health.