Glucagon-like peptide-1 (GLP-1) agonists are a class of medications designed to mimic a hormone naturally produced in the human gut. This hormone, GLP-1, is released by specialized cells in the intestine after a meal and plays a part in signaling fullness and managing blood sugar. In recent years, these drugs have moved into the public spotlight due to their applications in modern medicine.
How GLP-1 Agonists Function in the Body
When a person eats, the natural GLP-1 hormone is secreted from the small intestine and carries out several functions. It travels to the pancreas, where it sends signals to help regulate blood glucose. GLP-1 agonists are synthetic versions of this hormone, engineered to bind to the same cellular receptors and replicate these natural processes, often for a longer duration than the body’s own GLP-1.
A primary mechanism of these drugs involves the pancreas. GLP-1 agonists stimulate the pancreatic beta cells to release insulin in a glucose-dependent manner. This means they prompt insulin secretion when blood sugar levels are high, which helps move glucose from the blood into cells for energy. At the same time, they suppress the release of glucagon, which normally tells the liver to release stored glucose, preventing an unnecessary rise in blood sugar.
Another action of GLP-1 agonists occurs in the digestive tract. They slow down gastric emptying, which is the rate at which food moves from the stomach into the small intestine. By extending the time food remains in the stomach, they help to flatten the curve of post-meal blood sugar spikes. This delay also contributes to a prolonged feeling of fullness, or satiety, after eating.
These medications also exert influence on the central nervous system. GLP-1 receptors are found in areas of the brain, including the hypothalamus, that regulate appetite and food intake. The agonist drugs cross the blood-brain barrier and activate these receptors, sending signals to the brain that enhance feelings of satiety and reduce hunger sensations, which can lead to a reduction in overall calorie consumption.
Primary Medical Uses
The biological actions of GLP-1 agonists make them suitable for treating specific metabolic conditions. Their most established use is in the management of type 2 diabetes. The ability of these drugs to enhance insulin secretion and suppress glucagon in response to high blood sugar directly addresses the core issues of this condition. By improving glycemic control, they help lower hemoglobin A1c levels, a marker for long-term blood sugar management.
The American Diabetes Association recommends GLP-1 agonists as a potential first-line therapy for individuals with type 2 diabetes who also have or are at high risk for atherosclerotic cardiovascular disease. This recommendation is based on evidence showing that some of these medications can reduce the risk of major adverse cardiovascular events.
These medications are also approved for chronic weight management in individuals with obesity or who are overweight with at least one weight-related comorbidity. This application stems from their effects on appetite and digestion, which can lead to reduced caloric intake and result in significant weight loss over time.
The effectiveness of GLP-1 agonists in promoting weight loss has positioned them as a notable option for individuals who have struggled to lose weight through diet and exercise alone. The weight reduction they facilitate can also lead to improvements in other health markers, such as blood pressure and cholesterol levels.
Commonly Prescribed GLP-1 Medications
Several GLP-1 agonist medications are available, each with specific characteristics and approved uses. One well-known example is semaglutide, which is marketed under different brand names.
- Ozempic is an injectable form of semaglutide approved for the treatment of type 2 diabetes.
- Wegovy contains a higher dose of semaglutide and is specifically approved for chronic weight management.
- Rybelsus, an oral version of semaglutide, is also available for type 2 diabetes, offering an alternative to injections.
Another prescribed medication is liraglutide. It is sold as Victoza for the management of type 2 diabetes and as Saxenda for chronic weight management. Both Victoza and Saxenda are administered as a daily injection. Exenatide, available as a twice-daily injection (Byetta) or a once-weekly injection (Bydureon), is another option for type 2 diabetes.
A newer development in this area is the introduction of dual-agonist medications. Tirzepatide, sold under the brand name Mounjaro, is one such example. It acts on both the GLP-1 and the GIP (glucose-dependent insulinotropic polypeptide) receptors. By targeting both pathways, tirzepatide has shown significant efficacy in both blood sugar control for type 2 diabetes and in promoting weight loss.
These medications differ in their active ingredients, dosing schedules, and primary indications. For instance, dulaglutide (Trulicity) is another once-weekly injection for type 2 diabetes. The choice of medication often depends on the patient’s specific condition, as well as physician and patient preference regarding the frequency of administration.
Side Effects and Safety Considerations
While GLP-1 agonists are effective, they are associated with a range of potential side effects. The most commonly reported issues are gastrointestinal in nature. Patients frequently experience nausea, vomiting, diarrhea, constipation, and abdominal pain, particularly when first starting the medication or after a dose increase. These symptoms are often transient and may lessen as the body adjusts.
There are also more serious, though less common, risks associated with this class of drugs. All GLP-1 agonists carry a boxed warning from the FDA regarding a potential risk of thyroid C-cell tumors. This warning is based on studies in rodents where the drugs caused an increase in these types of tumors; however, it is not known if this risk translates to humans. Patients with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 are advised against using these medications.
Other safety concerns include the risk of pancreatitis, which is an inflammation of the pancreas that can be severe. Gallbladder problems, including gallstones, have also been reported in patients using these drugs. In some cases, patients have experienced severe gastroparesis, a condition where the stomach empties too slowly, which can lead to persistent nausea and vomiting.
Administration and Treatment Process
Most GLP-1 agonists are administered via subcutaneous injection, meaning they are injected into the fatty tissue just under the skin. Patients are trained to self-administer the medication using a pre-filled pen device. Common injection sites include the abdomen, thigh, or upper arm. The frequency of these injections varies by drug, with some requiring daily administration while others are given once a week.
The treatment process involves dose titration. Patients begin with a low starting dose, which is gradually increased over a period of several weeks or months. This slow escalation helps the body acclimate to the medication and is a strategy for minimizing the common gastrointestinal side effects like nausea. The final maintenance dose will vary depending on the specific medication and the individual patient’s response and tolerance.
These medications are intended for long-term use. For conditions like type 2 diabetes and chronic weight management, GLP-1 agonists are not considered a short-term fix. Continuous treatment is necessary to maintain the benefits of blood sugar control and weight management. Discontinuing the medication will result in the return of previous symptoms or weight regain.