Discover the Truth About Weight Loss Droplets: Do They Really Work?

The emergence of oral semaglutide has presented a novel approach to weight loss, offering a convenient alternative to injections. This article delves into the effectiveness, benefits, and considerations surrounding oral semaglutide, particularly in droplet form, drawing upon available research and expert opinions.

Understanding Semaglutide

Semaglutide belongs to a class of medications called glucagon-like peptide-1 (GLP-1) receptor agonists. GLP-1 is a hormone naturally produced in the small intestine, playing a crucial role in regulating various bodily functions, including slowing digestion, reducing hunger, increasing feelings of fullness, enhancing insulin sensitivity, managing blood sugar levels, and decreasing food chatter and food noise.

For many individuals, the GLP-1 hormone may not function optimally, particularly in those with Type 2 diabetes, where the body's ability to use insulin effectively is compromised, leading to elevated blood sugar levels. Originally developed for managing Type 2 diabetes, GLP-1 medications have demonstrated broader benefits, especially in weight management, regardless of whether an individual has Type 2 diabetes. Beyond weight loss, GLP-1s can have other long-term health benefits, including improving cholesterol levels, improving fatty liver disease, reducing your risk of heart disease and kidney disease, and reducing alcohol intake and smoking.

Oral Semaglutide: How It 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. However, when administered orally, semaglutide is dosed differently due to variations in absorption and delivery compared to injectable semaglutide.

Oral semaglutide is available in two primary forms:

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Tablets or pills: These are swallowed and currently represented by Rybelsus, a brand-name semaglutide tablet not yet available in generic form.
Drops: These are placed under the tongue, also known as sublingual semaglutide.

How to Take Oral Semaglutide or Tirzepatide Drops

For optimal efficacy, oral semaglutide needs to be taken once daily on an empty stomach, ideally early in the day. If this isn't feasible, it should be taken at least 30 minutes after eating.

Instructions for taking oral semaglutide drops:

Roll the bottle between your hands or shake lightly before each use.
Measure the prescribed amount in the oral syringe.
Place the liquid under your tongue (the solution has a peppermint flavor to make it more pleasant).
While keeping your mouth closed and relaxed, hold it there for at least 1-2 minutes (longer is better for absorption). Then swish it around your mouth before swallowing.
Avoid eating, drinking, or brushing your teeth for about 30 minutes after. This gives the medication time to absorb fully.

Oral vs. Injectable Semaglutide: A Comparative Analysis

The primary distinction between oral and injectable semaglutide lies in how their delivery methods impact the body's absorption of the drug, influencing efficacy and outcomes.

Research suggests that all forms of semaglutide can aid in weight loss, but the extent of weight loss varies.

Injectables: A study in the New England Journal of Medicine revealed that overweight or obese adults who injected semaglutide weekly experienced nearly 15% body weight loss after 68 weeks. For a 200-pound individual, this translates to a 30-pound weight loss.
Oral Tablets: One study reported an average weight loss of approximately 9 pounds after 26 weeks with oral semaglutide tablets. However, a recent study on orforglipron, an investigational pill, demonstrated that individuals with Type 2 diabetes experienced lowered blood sugar levels and weight loss of up to 16 pounds over 40 weeks, comparable to Ozempic results.
Oral Drops: Research on the effectiveness of oral drops is still in its early stages, but one animal study suggests it may be more effective than tablets, contingent on the duration the drug is held under the tongue for absorption before swallowing.

Ava Mainieri, PhD, Director of Clinical Outcomes and Programming at Midi Health, notes that there is currently no large-scale outcomes data on sublingual GLP-1s. However, preclinical and pharmacokinetic data indicate its similarity with FDA-approved GLP-1s. Animal models have shown that it works similarly, and pharmacokinetic data confirms that the sublingual drops are absorbed into the body.

While oral semaglutide may yield results, they may be slower and less dramatic compared to injectables. However, it may also result in fewer side effects, making it a potentially suitable long-term solution for individuals who prefer to avoid injections.

Switching from Injected GLP-1s to Oral Drops

For individuals who no longer wish to continue weekly injections or have achieved their desired weight loss, oral semaglutide drops can serve as a viable alternative for long-term weight management. It can be taken in a standard dose or via microdosing, involving a lower amount than the manufacturer's recommended dosage for weight loss while still potentially yielding results.

Dr. Mainieri suggests that sublingual semaglutide may be effective for maintaining weight loss achieved through injectable semaglutide or tirzepatide.

Who Should Consider Oral Semaglutide Drops?

Dr. Mainieri advises that oral semaglutide drops are not recommended for patients seeking to control diabetes or lose significant amounts of weight. In such cases, injectables offer the most substantial health benefits and glucose control.

Sublingual semaglutide is more appropriate for individuals aiming to lose a smaller amount of weight or explore the broader benefits of GLP-1s beyond diabetes control and major weight loss.

Key Differences: Oral Drops vs. Injectable Semaglutide

Oral semaglutide is best administered sublingually for absorption in the mouth and taken daily, whereas injectable semaglutide is administered once weekly and absorbed gradually throughout the week.

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Absorption & Bioavailability

Bioavailability refers to the proportion of the drug that successfully enters the bloodstream and becomes active in the body after administration. It is a crucial measure in pharmacology, indicating how much of a given dose of a drug is available to produce a therapeutic effect. High bioavailability ensures that patients are getting the maximum benefit from each dose, which is crucial for medications designed to manage chronic health conditions.

Different forms of semaglutide exhibit varying percentages of bioavailability:

Injectables: High bioavailability, approximately 89%.
Oral Tablets: Lower bioavailability due to metabolism in the stomach and exposure to stomach acids, ranging from 0.4% to 1% after full absorption.
Oral Drops: Drug absorption through tissues under the tongue bypasses much of the digestive system, potentially improving bioavailability compared to standard oral tablets, with estimates as high as 40%.

Convenience

Oral semaglutide presents a more convenient and less invasive option for individuals averse to injections. However, it necessitates strict adherence to dosing instructions to enhance absorption and efficacy. Conversely, injectable semaglutide is administered weekly as a quick injection, which some may find more manageable, although it requires refrigeration, potentially complicating travel. Tablets or drops offer greater portability and eliminate concerns about missing a dose.

Effectiveness

Animal studies have shown variable weight loss results with oral drops, and individual responses may vary depending on how long the drops are held under the tongue. Injectable semaglutide has demonstrated more consistent absorption and long-term efficacy.

The Role of Oral Semaglutide Drops During Perimenopause & Menopause

During perimenopause, estrogen levels fluctuate and decline, impacting the entire body. Since estrogen plays a role in weight control by helping to curb appetite, declining levels during perimenopause can lead to increased hunger and difficulty maintaining or losing weight. Other menopause symptoms, such as poor sleep and mood changes, can also trigger cravings for sugary, comfort foods.

Semaglutide can help during menopause by quieting food cravings and reducing the amount of time spent thinking about food. Personalized GLP-1 prescriptions are most effective when combined with a healthy diet and regular exercise.

Semaglutide for Anti-Aging and Longevity

Emerging research suggests that GLP-1s may have a profound impact on long-term health, potentially counteracting the effects of depleted estrogen in several ways:

Fewer heart issues: By improving glucose metabolism, reducing inflammation, and aiding in the maintenance of lean body mass, semaglutide could potentially lower the risk of age-related diseases such as cardiovascular conditions, like heart disease, high blood pressure, and stroke.
Lower risk of memory loss and dementia: GLP-1 receptor agonists like semaglutide may have neuroprotective effects, potentially reducing the risk of neurodegenerative diseases such as Alzheimer's.
Longer, healthier life: Semaglutide may contribute to longevity by mitigating factors like oxidative stress and chronic inflammation, both of which are linked to aging.

Dr. Mainieri emphasizes that current knowledge regarding longevity is primarily based on injectables, suggesting that some level of the same benefit could be applied to sublingual semaglutide.

Potential Side Effects and Risks of Oral Semaglutide

All forms of GLP-1s carry the risk of some side effects. The most frequently reported side effects are gastrointestinal, including:

Nausea
Diarrhea
Constipation

Serious risks to watch for include:

Pancreatitis (severe abdominal pain)
Thyroid tumors
Hypoglycemia
Gallstones or acute cholecystitis

If any of these issues arise, it's crucial to consult a healthcare provider immediately.

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 to support weight loss goals.

Dietary Changes: Focus on high-protein, fiber-rich foods to enhance satiety. Limit ultra-processed and high-sugar meals to optimize results.
Exercise for Enhanced Results: Strength training and cardiovascular exercise improve fat loss and preserve muscle mass.
Lifestyle Adjustments: Prioritize sleep, hydration, and stress management to maximize medication efficacy.

The Controversy of HCG for Weight Loss

It's important to distinguish semaglutide from other weight loss "aids" that have been promoted in the past, such as HCG (human chorionic gonadotropin). HCG is a hormone that supports the normal development of an egg in a woman’s ovary and stimulates the release of the egg during ovulation. While HCG is used to cause ovulation and to treat infertility in women, and to increase sperm count in men, it has also been marketed as a weight loss aid.

HCG and Weight Loss: Separating Fact from Fiction

Taking HCG in any form does not result in weight loss. The methods used alongside HCG are what might result in weight loss-such as a very-low-calorie-diet (VLCD). The decrease in hunger emphasized in HCG ads is likely attributed to the dietary emphasis on higher protein intake and/or carbohydrate restriction resulting in ketosis.

Methods of Taking HCG

HCG is typically taken as drops, but also some are prescribed tablets or injections. There is a “ceiling” with regard to the size of a molecule that can be absorbed orally-and that size is approximately 1500 daltons (a measure for molecular weight). HCG’s molecular weight is approximately 30,000 daltons-about six times larger than insulin, which measures in at 6,000 daltons. Therefore, since HCG’s molecular weight is six times that of insulin, which can’t be absorbed orally, neither can HCG be absorbed orally.

Even if drop formulations actually contained HCG, the protein molecule would pass into the stomach where it would be broken down into small peptides and amino acids by gastric acid-just like your dinner portion of chicken-again, no potential for biological action!

HCG can be given by injection by a licensed physician under “off-label” use. However, doing so is not risk free. This medicine can increase chances of a multiple pregnancy. Some women using this medicine have developed a condition called ovarian hyperstimulation syndrome (OHSS), especially after the first treatment cycle. You should NOT use this medicine if you are at risk for a hormone-related cancer such as tumor of the breast, ovary, uterus, prostate, hypothalamus, or pituitary gland.

Homeopathy is based the belief that disease symptoms can be cured by small doses of substances which produce similar symptoms in healthy people. All HCG drop formulations are inert, or having no pharmacological action, due to their high molecular weight. Moreover, it is the specific shape and structure of a molecule on which the hormone’s action depends. Therefore, it would be impossible to “take a small dose” or “a segment” of a hormone and expect to cause any kind of biological action.

The Food and Drug Administration, The Federal Trade Commission, and The American Society for Metabolic & Bariatric Surgery all share the same stance: HCG does not result in weight loss.

Microbeads: A Novel Approach to Fat Blocking

Researchers are exploring alternative methods for weight loss, including fat-blocking microbeads made with green tea, vitamin E, and seaweed. These microbeads could offer a new way to lose weight and a potential alternative to popular GLP-1 drugs and bariatric surgery.

While human trials are still needed, scientists in China found that rats fed a high-fat diet lost about 17% of their body weight when given the edible microbeads. The rats also saw reduced fat tissue, alleviated liver damage and lowered blood fat levels compared to animals that did not receive the beads.

The microbeads are made from green tea polyphenols - antioxidants in tea leaves - combined with vitamin E to bind to fat droplets in the gut and block their absorption. A seaweed-derived coating protects the beads from stomach acid. The nearly flavorless beads could be integrated into everyday foods, and even formed into tapioca-like balls for desserts or bubble teas.

The experimental microbeads appeared to curb fat and weight gain without disrupting blood sugar, digestion or energy levels.

The Rise of GLP-1 Supplements and the Importance of Regulation

As the Food and Drug Administration cracks down on compounded versions of popular weight loss drugs Wegovy (semaglutide) and Zepbound (tirzepatide), some individuals may be drawn to dietary supplements that claim to “complement” or “supercharge” the body’s levels of the gut hormone GLP-1.

However, it's crucial to exercise caution when considering these supplements. So-called GLP-1 supplements are likely to be ineffective for weight loss. “If you can buy it without a prescription, it’s not an actual GLP-1 drug,” Alan said. “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.”

The FDA doesn’t regulate dietary supplements for safety or effectiveness before they hit the market, whether they’re a daily multivitamin or a post-workout protein powder. For that reason, the agency advises consulting a health care provider before adding any supplement to your regimen.

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