As the Food and Drug Administration (FDA) increases its scrutiny of compounded versions of popular weight loss drugs like Wegovy (semaglutide) and Zepbound (tirzepatide), many Americans who depend on these more affordable alternatives may find themselves drawn to a questionable segment of the dietary supplement market. These supplements, ranging from colorful patches and fruit punch-flavored gummies to prebiotic powders and under-the-tongue tinctures, often claim to "complement" or "supercharge" the body's levels of the gut hormone GLP-1. Unlike compounded drugs, which require a consultation with a clinician to obtain a prescription, supplements are readily available over the counter.
The Allure and Deception of GLP-1 Supplements
The marketing of these GLP-1 supplements can be misleading. Jamie Alan, an associate professor of pharmacology and toxicology at Michigan State University’s College of Human Medicine, suggests that these supplements are likely ineffective for weight loss. According to Alan, "If you can buy it without a prescription, it’s not an actual GLP-1 drug. It is something else that’s marketed to support your endogenous GLP-1 production. These things are just older weight loss [supplements] that are rebranded, and there’s really no scientific evidence for these.”
Ingredients like ashwagandha and green tea extract, which have been used in diet products for decades, are being recycled in these GLP-1 supplements. While ashwagandha is often promoted as a stress reliever, and cortisol (a stress hormone) can be linked to weight gain, there is limited evidence that the evergreen shrub directly aids in weight loss. Green tea and green tea extract may have a "possible modest effect on body weight," but research is mixed, and some studies link the extract to liver damage, according to the Office of Dietary Supplements.
Disclaimers and Missing Ingredients
Many brands are careful to include disclaimers that their products do not contain synthetic GLP-1 or act as GLP-1 agonists. For example, Kind Patches explicitly states that its GLP-1 adhesive "does not contain synthetic GLP-1 and is not a GLP-1 agonist drug." Similarly, Lemme, Kourtney Kardashian Barker’s wellness brand, features an identical disclaimer for its GLP-1 Daily Support Capsules. Trim Biome GLP-1, manufactured by Inno Supps, highlights "clinically studied ingredients" but not the hormone itself.
Jeff Ventura, the vice president of communications for the Council for Responsible Nutrition, a trade group for the supplement industry, stated that there are “no direct comparators” for GLP-1 drugs in the dietary supplement industry. He admits that while some supplement ingredients have shown promise in limited studies related to metabolic health and weight management, they do not have the same effects as GLP-1 drugs.
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The FDA's Role and Consumer Risk
The FDA does not regulate dietary supplements for safety or effectiveness before they are marketed, which means that whether it’s a daily multivitamin or a post-workout protein powder, supplements are not vetted before hitting shelves. For this reason, the agency advises consulting a health care provider before adding any supplement to your regimen. According to Alan, "There could be harm in some of these. There are going to be some people who might have a significant drug interaction, who might have a significant medical condition. In most people there’s probably minimal risk of harm, but that’s not true for everyone.”
The Rise and Fall of Compounded GLP-1 Drugs
GLP-1 drugs have been used to treat Type 2 diabetes since 2005, but demand soared after the FDA approved Wegovy and Zepbound for weight loss in 2021 and 2023, respectively. The resulting shortages allowed compounding pharmacies to produce "essentially copies" of commercially available drugs. These compounded versions of Wegovy and Zepbound became popular because they were generally sold for less than the brand-name drugs.
However, the FDA declared the tirzepatide shortage over in December and the semaglutide shortage in February, requiring compounders to pull their products from the market. This creates an opportunity for GLP-1 supplement sellers to flood the market, potentially misleading consumers into thinking that unproven patches can deliver the same results as clinically tested drugs.
Dr. W. Scott Butsch, director of obesity medicine at the Cleveland Clinic Bariatric and Metabolic Institute, notes that the FDA has stated very clearly that compounded versions are not the same, do not have the same ingredients, and have not been tested. He also expresses concern that compounders and supplement companies are using lower pricing to target a vulnerable clientele with poor access to obesity medications, preying on the desperate who think they can save money and still get the benefit.
Expert Opinions and Dietary Alternatives
According to Dr. Dariush Mozaffarian, a cardiologist and the director of Tufts University’s Food Is Medicine Institute, there’s no simple dietary fix that’s going to do what these drugs do in a short amount of time. However, he acknowledges the potential of boosting natural GLP-1 production through diet. Healthy fats and high-fiber foods have been shown to trigger GLP-1 production, though its natural release into the bloodstream is fleeting compared to the sustained action of GLP-1 drugs.
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Mozaffarian suggests focusing on healthy food rather than spending money on supplements, stating that it's too early for GLP-1 supplements to have substantial scientific backing. Alan, of Michigan State University, is even more direct, calling these supplements "snake oil" and a waste of money.
A Closer Look at Weight Loss Supplements
The promise of fast and easy weight loss through supplements is tempting, but it's essential to understand that dietary supplements are not medicines and are not subject to the same rigorous testing and approval processes as drugs. Companies that make supplements are responsible for ensuring their safety, but the FDA does not need to approve them before they are sold. Clinical trials for dietary supplements are rare, and even when they exist, they may be small and of short duration, making it difficult to predict real-life results.
It's also important to recognize that "natural" does not automatically equate to "safe." Supplements can have strong effects, and some weight-loss supplements have been found to contain unlisted ingredients, including prescription medicines. The key to losing weight and maintaining overall health is a comprehensive lifestyle approach that includes a balanced diet and regular physical activity.
FDA Public Notifications: A History of Hidden Ingredients
The FDA has issued numerous public notifications over the years about weight loss supplements found to contain hidden and potentially harmful drug ingredients. These notifications serve as a stark reminder of the risks associated with unregulated supplements and the importance of exercising caution when considering such products.
Oral Semaglutide: An Alternative to Injections
Oral semaglutide has emerged as a convenient alternative to injections for weight loss. Working with a healthcare professional can help determine if a personalized GLP-1 prescription is appropriate and which form may be best suited to individual goals, preferences, and health history.
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What is Semaglutide?
Semaglutide belongs to a class of medications known as glucagon-like peptide-1 (GLP-1) receptor agonists. These medications mimic the GLP-1 hormone naturally produced in the small intestine, which slows digestion, reduces hunger, increases feelings of fullness, enhances insulin sensitivity, manages blood sugar levels, and decreases food chatter and food noise.
How Oral Semaglutide Works
Oral semaglutide contains the same active ingredient as injectable GLP-1s, working to slow digestion, reduce appetite, regulate insulin sensitivity, and support weight loss. It is available in tablet form (Rybelsus) and as drops placed under the tongue (sublingual semaglutide).
How to Take Oral Semaglutide Drops
For best efficacy, oral semaglutide drops should be taken once daily on an empty stomach, ideally early in the day. The prescribed amount should be measured in an oral syringe, placed under the tongue, and held there for 1-2 minutes to allow for absorption. Eating, drinking, or brushing teeth should be avoided for about 30 minutes after taking the drops.
The Effectiveness of Oral vs. Injectable Semaglutide
Research suggests that all forms of semaglutide can aid in weight loss, but the extent of weight loss varies. Injectable semaglutide has demonstrated significant weight loss in studies, while oral tablets have shown more modest results. Research on the efficacy of oral drops is still emerging, but some studies suggest it may be more effective than tablets, depending on absorption time.
Oral semaglutide drops may be a good alternative for long-term weight management, particularly for those who have grown tired of weekly injections or have reached their desired weight loss. Some evidence suggests that sublingual semaglutide may be efficacious for maintaining weight loss achieved with injectable semaglutide or tirzepatide.
Who Should Consider Oral Semaglutide Drops?
Oral semaglutide drops are not recommended for patients looking to control diabetes or lose large amounts of weight. They are more suitable for individuals who want to lose a smaller amount of weight or explore the other benefits of GLP-1s beyond diabetes control and major weight loss.
Key Differences Between Oral Drops and Injectable Semaglutide
The main differences between oral and injectable semaglutide lie in their delivery methods, which affect the body's absorption of the drug, impacting efficacy and results.
Absorption and Bioavailability
Bioavailability, the proportion of the drug that successfully enters the bloodstream and becomes active in the body, varies among the different forms of semaglutide:
- Injectables: High bioavailability, around 89%.
- Oral Tablets: Lower bioavailability due to metabolism in the stomach, ranging from 0.4% to 1%.
- Oral Drops: Higher bioavailability compared to tablets, potentially as high as 40%, as the drug is absorbed through the tissues under the tongue, bypassing much of the digestive system.
Convenience
Oral semaglutide can be a more convenient option for individuals averse to injections, but it requires strict adherence to dosing instructions. Injectable semaglutide is administered weekly but requires refrigeration, which can be less convenient for travel.
Effectiveness
Injectable semaglutide has been shown to offer more consistent absorption and long-term efficacy, while animal studies show variable weight loss results for oral drops.
Potential Side Effects and Risks of Oral Semaglutide
All forms of GLP-1s carry the risk of side effects, most commonly gastrointestinal issues such as nausea, diarrhea, and constipation. Serious risks to watch for include pancreatitis, thyroid tumors, hypoglycemia, and gallstones.
Combining Oral Semaglutide with Other Weight Loss Strategies
To maximize the benefits of weight-loss medications, it's essential to reshape diet and exercise routines. Focus on high-protein, fiber-rich foods, limit ultra-processed and high-sugar meals, and incorporate strength training and cardiovascular exercise. Prioritizing sleep, hydration, and stress management can also maximize medication efficacy.
Semaglutide for Anti-Aging and Longevity
Emerging research suggests that GLP-1s can have a profound impact on long-term health, potentially counteracting the effects of depleted estrogen and reducing the risk of age-related diseases such as cardiovascular conditions and neurodegenerative diseases. Early studies indicate that semaglutide may contribute to longevity by mitigating factors like oxidative stress and chronic inflammation.