GLP-1

Quick definition. GLP-1 is a gut hormone that triggers insulin release after meals. This page defines the hormone. For the full guide to GLP-1 medications — all 11 FDA-approved drugs, how they compare, and how to choose — see What Are GLP-1 Medications?

The Incretin System

The incretin system is the body's built-in mechanism for managing post-meal blood sugar. Two primary incretin hormones drive this system: GLP-1 and GIP (glucose-dependent insulinotropic polypeptide). Together, these hormones are responsible for a significant portion of the insulin response that occurs after eating. In people with type 2 diabetes, the incretin system is often impaired, which contributes to poor blood sugar control.

How GLP-1 Receptor Agonists Work

GLP-1 receptor agonists (GLP-1 RAs) are medications designed to mimic or enhance the effects of natural GLP-1. They work through several mechanisms:

• Insulin secretion: GLP-1 RAs stimulate the pancreas to release insulin in a glucose-dependent manner, meaning they primarily act when blood sugar is elevated. This reduces the risk of dangerously low blood sugar (hypoglycemia) compared to some other diabetes medications.
• Glucagon suppression: These medications reduce the release of glucagon, a hormone that raises blood sugar. By lowering glucagon levels after meals, GLP-1 RAs help prevent blood sugar spikes.
• Slowed gastric emptying: GLP-1 RAs slow the rate at which food leaves the stomach, leading to a more gradual rise in blood sugar after eating and contributing to feelings of fullness.
• Appetite reduction: GLP-1 RAs act on receptors in the brain, particularly in areas that regulate hunger and satiety. This effect is a key reason these medications have shown significant results for weight management.

FDA-Approved GLP-1 Receptor Agonists

The following GLP-1 RA medications have received FDA approval, listed with their generic names and brand names:

• Exenatide -- Byetta (twice daily), Bydureon (once weekly)
• Liraglutide -- Victoza (diabetes), Saxenda (weight management)
• Dulaglutide -- Trulicity (once weekly)
• Semaglutide -- Ozempic (injectable, diabetes), Wegovy (injectable, weight management), Rybelsus (oral, diabetes)
• Lixisenatide -- Adlyxin
• Tirzepatide -- Mounjaro (diabetes), Zepbound (weight management)

Note: Tirzepatide is a dual GIP/GLP-1 receptor agonist, meaning it targets both incretin receptors. It is sometimes grouped with GLP-1 RAs but has a distinct mechanism.

A Brief History

The development of GLP-1 receptor agonists spans nearly two decades:

• 2005: Exenatide (Byetta) became the first FDA-approved GLP-1 RA, initially derived from a compound found in Gila monster venom.
• 2010: Liraglutide (Victoza) was approved for type 2 diabetes, offering once-daily dosing.
• 2014: Liraglutide received a separate approval as Saxenda for chronic weight management.
• 2017: Semaglutide (Ozempic) was approved for type 2 diabetes, with once-weekly dosing.
• 2021: Semaglutide received approval as Wegovy for weight management at a higher dose.
• 2022: Tirzepatide (Mounjaro) was approved for type 2 diabetes, introducing the first dual GIP/GLP-1 receptor agonist. Tirzepatide later received approval as Zepbound for weight management in 2023.

These medications represent a significant advancement in the treatment of type 2 diabetes and obesity. However, they are prescription medications with potential side effects and are not appropriate for everyone. Individuals should consult a qualified healthcare provider to determine whether a GLP-1 RA may be suitable for their specific medical needs.