Glucagon-Like Peptide-1 (GLP-1) is a naturally occurring hormone that plays a significant role in the body’s metabolic processes. It is a peptide hormone, composed of a short chain of amino acids.
What GLP-1 Does Naturally
Naturally occurring GLP-1 is primarily produced by specialized L-cells, found predominantly in the lining of the small intestine, particularly in the distal ileum and colon, but also in the jejunum and duodenum. Its release is stimulated by the presence of nutrients in the gut after food consumption, occurring in a biphasic pattern. This hormone acts as an incretin, meaning it enhances the secretion of insulin from the pancreas in a glucose-dependent manner, helping to lower blood sugar levels only when they are elevated.
Beyond stimulating insulin, GLP-1 also suppresses the release of glucagon, a hormone that raises blood glucose. It slows down the rate at which food leaves the stomach, known as gastric emptying. This delays gastric emptying, contributing to a prolonged feeling of fullness. It also signals to the brain’s appetite centers, promoting satiety and reducing overall food intake.
How GLP-1 Inspired Medications
The diverse physiological actions of natural GLP-1, particularly its effects on glucose regulation and appetite, led scientists to recognize its potential for therapeutic applications. However, a significant challenge was the natural hormone’s very short half-life in the bloodstream, around two minutes, due to rapid degradation by an enzyme called dipeptidyl peptidase-4 (DPP-4). This rapid breakdown made it impractical for direct medical use as a sustained treatment.
To overcome this, researchers developed GLP-1 receptor agonists, also called GLP-1 analogs or incretin mimetics. These synthetic compounds mimic natural GLP-1’s structure and function. They activate the same GLP-1 receptors, initiating similar biological responses. These medications are designed to resist DPP-4 degradation, providing a much longer duration of action, from hours to days. This extended activity allows for sustained therapeutic effects, making them viable treatments for various conditions.
The Impact of GLP-1 Medications
GLP-1 receptor agonist medications have significantly impacted modern medicine, primarily in managing Type 2 Diabetes and obesity. For Type 2 Diabetes, these medications improve blood sugar control by stimulating insulin release and suppressing glucagon. This occurs only when glucose levels are elevated, minimizing the risk of low blood sugar. They have been shown to reduce hemoglobin A1C, a measure of average blood sugar over two to three months, by approximately 0.8% to 1.6%.
For obesity or excess weight, GLP-1 medications contribute to weight loss by promoting fullness and slowing gastric emptying. Clinical studies have demonstrated an average weight loss ranging from 5% to over 20% of initial body weight, depending on the specific medication and treatment duration.
Beyond glucose and weight management, some GLP-1 receptor agonists also show broader health benefits. These include a reduced risk of major adverse cardiovascular events, heart failure, and cardiovascular death in certain patient populations. They may also contribute to lowering blood pressure and improving lipid profiles. Some medications have also received approval for slowing kidney disease progression in individuals with Type 2 Diabetes.