From the Guidelines
Yes, there are naturally occurring Glucagon-like peptide-1 (GLP-1) agonists. The primary natural GLP-1 agonist is GLP-1 itself, which is produced by intestinal L-cells in response to food intake, particularly carbohydrates and fats. Natural GLP-1 exists in two forms: GLP-1(7-36) amide and GLP-1(7-37), with the amidated form being the predominant circulating form in humans. These endogenous GLP-1 molecules bind to GLP-1 receptors in the pancreas, brain, heart, and other tissues to regulate glucose metabolism, appetite, and various physiological functions. However, natural GLP-1 has a very short half-life (1-2 minutes) because it is rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4) 1. This short duration of action limits the therapeutic utility of natural GLP-1, which is why pharmaceutical companies have developed modified GLP-1 receptor agonists like exenatide, liraglutide, and semaglutide that resist enzymatic degradation and have longer half-lives for treating diabetes and obesity. Some of the key benefits of GLP-1 receptor agonists include improved glycemic control, weight loss, and reduced risk of major adverse cardiovascular events, as demonstrated in several studies 2, 3, 4, 5. The use of GLP-1 receptor agonists is recommended for patients with type 2 diabetes and established cardiovascular disease or at high risk of cardiovascular events. It is essential to note that while natural GLP-1 has a short half-life, the development of modified GLP-1 receptor agonists has significantly improved the treatment options for patients with diabetes and obesity. The most recent studies, such as the 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS guideline, highlight the importance of GLP-1 receptor agonists in reducing major adverse cardiovascular events in patients with type 2 diabetes and cardiovascular disease 5. In summary, naturally occurring GLP-1 agonists play a crucial role in regulating glucose metabolism and appetite, and the development of modified GLP-1 receptor agonists has revolutionized the treatment of diabetes and obesity.
From the FDA Drug Label
Liraglutide is an acylated human Glucagon-Like Peptide-1 (GLP-1) receptor agonist with 97% amino acid sequence homology to endogenous human GLP-1(7-37). GLP-1(7-37) represents <20% of total circulating endogenous GLP-1
Naturally occurring GLP-1 agonists are present in the human body, specifically GLP-1(7-37), which has a similar effect to liraglutide on the GLP-1 receptor.
- GLP-1(7-37) is an endogenous peptide with a half-life of 1.5-2 minutes due to degradation by enzymes.
- It activates the GLP-1 receptor, leading to insulin release and glucagon secretion in a glucose-dependent manner. 6
From the Research
Naturally Occurring GLP-1 Agonists
- There are several naturally occurring compounds that have been found to have modulatory effects on GLP-1 expression and secretion, including: + Berberine + Tea + Curcumin + Cinnamon + Wheat + Soybean + Resveratrol + Gardenia 7
- These herbal-based constituents may exert an influence on GLP-1 release, although the exact mechanisms and effectiveness of these compounds are still being studied.
Comparison to Synthetic GLP-1 Receptor Agonists
- Synthetic GLP-1 receptor agonists, such as exenatide and liraglutide, have been shown to have potent hypoglycemic effects via several molecular pathways 8, 9
- While naturally occurring compounds may have potential as GLP-1 agonists, synthetic GLP-1 receptor agonists have been more extensively studied and are currently approved for the treatment of type 2 diabetes.
Potential Benefits and Limitations
- Naturally occurring GLP-1 agonists may offer a potential alternative to synthetic GLP-1 receptor agonists, although more research is needed to fully understand their effects and potential benefits 7
- The use of naturally occurring compounds as GLP-1 agonists may be limited by factors such as variability in composition and potency, as well as potential interactions with other medications.