GLP-1 (glucagon-like peptide-1) is a hormone vital for regulating blood sugar and controlling appetite, which is why it has gained attention in weight loss and diabetes treatments. Despite its importance, over-the-counter GLP-1 supplements are largely ineffective. Here’s why:

1. GLP-1 Is Broken Down Quickly: In the body, GLP-1 is rapidly degraded by enzymes such as DPP-4 (dipeptidyl peptidase-4). Over-the-counter supplements, usually in capsule or powder form, are subject to the same enzymatic breakdown, meaning they don’t last long enough to provide any real benefit.
2. Lack of Bioavailability: When GLP-1 is taken orally as a supplement, it is broken down in the digestive system like any other protein. This breakdown prevents enough active GLP-1 from entering the bloodstream to have a significant impact on metabolic processes, making oral supplements ineffective.
3. GLP-1 Receptors Are Found Throughout the Body: GLP-1 receptors are widespread, not only in the pancreas but also in the brain, heart, and gut. For GLP-1 to properly activate these receptors, it must be delivered in a form that reaches all these areas. Oral supplements lack the sophisticated delivery system needed to activate these receptors across the body, reducing their efficacy.
4. GLP-1 Supplements Cannot Stimulate K-Cells in the Small Intestine: K-cells in the small intestine naturally secrete GLP-1 in response to food, particularly after consuming fats and proteins. For instance, eating foods like avocado or steak triggers the release of GLP-1. This natural secretion occurs in response to nutrient signals in the gut, which supplements bypass. Because GLP-1 supplements don’t engage the digestive system’s K-cells, they fail to initiate the natural release of GLP-1 as food does.
5. GLP-1 Stimulates Insulin Release from the Pancreas: One of the key functions of GLP-1 is to stimulate the pancreas to release insulin. While this is crucial for regulating blood sugar levels, sustained or excessive GLP-1 activity—such as through prescription medications or overuse—can lead to excessive insulin secretion, a condition known as **hyperinsulinemia**. Chronically high insulin levels may contribute to **insulin resistance**, a condition in which the body’s cells become less responsive to insulin. Over time, this can increase the risk of developing type 2 diabetes and other metabolic conditions. Hyperinsulinemia has also been linked to health issues such as obesity, cardiovascular disease, and certain cancers. While this is primarily a concern with long-term use of GLP-1 medications, it underscores the risks of manipulating GLP-1 pathways without a full understanding of the potential consequences.
6. Prescription GLP-1 Medications Are More Effective: FDA-approved GLP-1 medications, such as semaglutide (Ozempic) and liraglutide (Saxenda), are specifically designed to bypass the issues that supplements face. These drugs are often injected to avoid digestive breakdown and ensure that the active GLP-1 reaches its target receptors throughout the body. However, even with these medications, there are concerns about prolonged insulin stimulation and the potential long-term health risks.
7. Unknown Long-Term Effects of Synthetic GLP-1: While synthetic GLP-1 medications are effective in the short term, their long-term impact remains uncertain. Prolonged activation of GLP-1 receptors and chronic insulin secretion may have unforeseen consequences, such as the development of insulin resistance or other metabolic disorders. More research is needed to fully understand the risks of long-term GLP-1 drug use.
8. Lack of Regulation and Efficacy: Over-the-counter GLP-1 supplements are not as strictly regulated as prescription medications. This raises concerns about their safety, efficacy, and even the authenticity of the ingredients. Without proper regulation and formulation, these supplements fail to deliver the intended benefits and can’t replicate the body’s natural processes for GLP-1 secretion and action.

In conclusion, while GLP-1 is a critical hormone for controlling blood sugar and appetite, over-the-counter supplements fail to mimic the body’s natural processes, such as stimulating K-cells to release GLP-1 in response to food. Moreover, prolonged GLP-1 activity through medications may lead to insulin overproduction, potentially causing insulin resistance and other metabolic disorders. Whole foods that naturally stimulate GLP-1 secretion, along with a balanced approach to prescription medications, remain the best strategy for managing blood sugar and weight in a healthy way.

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Robert Ferguson is a California- and Florida-based single father of two daughters, nutritionist, researcher, best-selling author, speaker, podcast and television host, health advisor, NAACP Image Award Nominee, creator of the Diet Free Life methodology, Chief Nutrition Officer for iCoura Health, and he serves on the Presidential Task Force on Obesity for the National Medical Association. You can e-mail Robert at robert@dietfreelife.com.