GLP-1, or glucagon-like peptide-1, is a hormone that helps regulate blood sugar and appetite. It is released after meals by L-cells in the intestine and acts on several organs to coordinate glucose control and food intake. Here’s a concise overview of how GLP-1 works, including what happens when GLP-1 receptor agonists (GLP-1 RAs) are used therapeutically. Key actions of natural GLP-1
- Pancreas: GLP-1 enhances glucose-dependent insulin secretion when blood glucose is elevated, helping lower post-meal blood sugar. It also suppresses glucagon release when glucose is high, reducing hepatic glucose production.
- Stomach: GLP-1 slows gastric emptying, which slows the rate at which glucose enters the bloodstream after a meal and promotes a feeling of fullness.
- Brain: By influencing appetite centers, GLP-1 contributes to reduced hunger and energy intake.
- Other tissues: GLP-1 can have modest effects on cardiovascular and gastrointestinal function, and may support beta-cell health over time.
How GLP-1 receptor agonists work (medications like Ozempic, Trulicity, Mounjaro, and others)
- Mechanism: These drugs mimic the action of endogenous GLP-1 by activating the GLP-1 receptor (GLP-1R), a G-protein–coupled receptor found in the pancreas, brain, stomach, and other tissues.
- Glucose control: By stimulating GLP-1R in a glucose-dependent manner, they increase insulin release when blood sugar is high, while having a limited effect when glucose is normal, reducing the risk of hypoglycemia relative to some other diabetes therapies.
- Glucagon suppression: They suppress glucagon release during hyperglycemia, reducing hepatic glucose output.
- Gastric emptying and satiety: They slow gastric emptying and promote satiety, which helps reduce appetite and total caloric intake, contributing to weight loss in many people.
- Beta-cell support: Some GLP-1 RAs may have beneficial effects on pancreatic beta-cell function and mass over time, though this is an area of ongoing research.
Clinical effects and considerations
- Indications: GLP-1 RAs are approved for type 2 diabetes management and, in several cases, for weight management in adults with obesity or overweight conditions, often with comorbidities.
- Benefits: Improved HbA1c, modest weight loss, potential cardiovascular benefits with certain agents.
- Side effects: Commonly include nausea, vomiting, diarrhea, and possible slowed gastric emptying. These effects tend to lessen over weeks for many patients. Rare events include gallbladder issues and pancreatitis concerns; monitoring and medical guidance are important.
- Dosing and administration: GLP-1 RAs are typically injected subcutaneously, with dosing schedules ranging from daily to weekly, depending on the specific product.
Important nuances
- Not a one-size-fits-all solution: Response can vary by agent, patient weight, coexisting conditions, and tolerance of GI side effects.
- Hypoglycemia risk: When used alone for diabetes, the risk of low blood sugar with GLP-1 RAs is relatively low due to glucose-dependent insulin secretion, but the risk increases if combined with other glucose-lowering medications like insulin or sulfonylureas.
- Cardiovascular considerations: Some GLP-1 RAs have demonstrated cardiovascular benefits in clinical trials, which can influence choice of therapy for patients with cardiovascular disease or risk.
If you’d like, I can tailor this to a specific GLP-1 RA (e.g., Ozempic vs. Victoza vs. Trulicity) or focus on how GLP-1–mediated mechanisms relate to blood sugar targets, weight loss expectations, or side-effect management.
