Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are gut hormones that regulate the body’s metabolism. They are naturally released in response to food intake, influencing how the body processes nutrients and manages energy.
Natural Roles in the Body
GLP-1 and GIP are incretin hormones, secreted by specialized cells in the intestine after food intake. GLP-1 is released from L cells in the lower intestine, and GIP from K cells in the upper small intestine. These hormones stimulate insulin release from pancreatic beta cells in a glucose-dependent manner, meaning insulin is released more effectively when blood sugar levels are elevated.
The “incretin effect” describes how oral glucose triggers a greater insulin response than intravenous glucose, largely due to GLP-1 and GIP. Beyond stimulating insulin, GLP-1 suppresses glucagon secretion, preventing excessive glucose production by the liver. GLP-1 also slows gastric emptying, contributing to feelings of fullness and reducing food intake. GIP enhances insulin secretion and can influence appetite, but has less effect on gastric emptying than GLP-1.
Therapeutic Development and Use
Understanding how natural GLP-1 and GIP regulate metabolism led to the development of medications that mimic or enhance their actions. GLP-1 receptor agonists activate the GLP-1 receptor, replicating many of the hormone’s effects. These medications are used to manage blood sugar levels in individuals with type 2 diabetes by promoting insulin release, reducing glucagon, and slowing digestion.
Some GLP-1 receptor agonists are also approved for weight management. Their effects on satiety and gastric emptying can lead to reduced food intake and subsequent weight loss. For instance, semaglutide, a GLP-1 receptor agonist, has shown an average weight loss of approximately 14.9% in clinical trials. Newer dual GLP-1/GIP receptor agonists, such as tirzepatide, activate both GLP-1 and GIP receptors. This dual action leads to more pronounced effects on blood sugar control and weight reduction, with tirzepatide demonstrating an average weight loss of around 20.9% in trials. These therapies represent a significant advancement in treating both type 2 diabetes and obesity.
Common Considerations and Side Effects
Individuals considering therapies that mimic GLP-1 and GIP should be aware of common considerations and potential side effects. Most of these medications are administered as subcutaneous injections, typically given in the abdomen, thigh, or upper arm. Some oral formulations are also available.
Common side effects often involve the gastrointestinal system, including nausea, vomiting, diarrhea, and constipation. These effects are generally mild to moderate and tend to decrease over time as the body adjusts to the medication. Patients should discuss their medical history and existing conditions with a healthcare provider to determine if these therapies are appropriate. These medications are not a standalone treatment and should be used with lifestyle and dietary changes for optimal outcomes in managing type 2 diabetes or obesity.