Oral semaglutide, known by its brand name Rybelsus, is a daily tablet approved to manage blood sugar in adults with type 2 diabetes. While its primary purpose is glycemic control, the medication has gained attention for its effect on body weight. This has led to its increasing off-label prescription for individuals seeking help with chronic weight management.
How Oral Semaglutide Promotes Weight Loss
Oral semaglutide facilitates weight loss because it is a glucagon-like peptide-1 (GLP-1) receptor agonist, mimicking the natural GLP-1 hormone released after a meal. By activating GLP-1 receptors, the medication signals the brain’s hypothalamus to regulate appetite, making you feel less hungry.
The medication also slows gastric emptying, the rate at which food moves from the stomach to the intestines. This delay contributes to a prolonged feeling of fullness after eating, which can lead to a natural reduction in calorie intake and the desire to eat large portions.
Some evidence also suggests that GLP-1 receptor agonists might influence food choices. The brain signaling prompted by the medication may also help reduce cravings for certain types of foods, particularly those high in fat.
Clinical Efficacy for Weight Management
The effectiveness of oral semaglutide for weight loss has been observed in clinical studies. In a six-month study of adults with type 2 diabetes, those taking the 14 mg dose of Rybelsus lost an average of 8 pounds, while those on a 7 mg dose lost around 5 pounds.
Research has also explored higher doses for weight management in people without diabetes. The OASIS 1 clinical trial found that a higher daily dose led to significant weight loss compared to a placebo. The STEP UP trial showed an average weight reduction of 20.7% after 72 weeks, which for a 250-pound person, translates to a loss of over 50 pounds.
These results are most pronounced when the medication is combined with lifestyle modifications like a reduced-calorie diet and increased physical activity. Individual results can vary, and sustained use appears necessary for maintaining weight loss. One study found that participants regained a significant portion of lost weight within a year of stopping the treatment.
Distinctions from Injectable Semaglutide
The primary difference between oral and injectable semaglutide is the administration method. Oral semaglutide (Rybelsus) is a daily tablet, while injectable forms like Ozempic and Wegovy are a once-weekly shot.
The dosage and absorption process also differ. Oral semaglutide comes in 3 mg, 7 mg, and 14 mg tablets, while injections offer different strengths, with Wegovy providing higher doses for weight management. The oral tablet is co-formulated with an absorption enhancer, sodium N-(8-[2-hydroxylbenzoyl] amino) caprylate (SNAC), to protect it from stomach acid and aid absorption.
Due to this complex process, less than 1% of the semaglutide in the tablet enters the body, requiring a daily dose. In contrast, the injectable form is absorbed more directly and efficiently, allowing for a longer-lasting effect from a single weekly dose. Some physicians note the higher blood levels from injections may lead to greater appetite control and more weight loss.
Common Side Effects and Safety Profile
The most common side effects of oral semaglutide are gastrointestinal. These symptoms are often most pronounced when starting the medication or after a dose increase and tend to lessen as the body adjusts. They include:
- Nausea
- Vomiting
- Diarrhea
- Abdominal pain
- Constipation
More serious risks exist, and Rybelsus has an FDA boxed warning for a potential risk of thyroid C-cell tumors. This is based on rodent studies, and it is unknown if the effect occurs in humans. It is contraindicated for individuals with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2.
Other serious side effects include pancreatitis, gallbladder problems, kidney issues, and gastroparesis (stomach paralysis). Pancreatitis can cause persistent, severe abdominal pain. Any severe or persistent symptoms should be discussed with a healthcare provider immediately.
Eligibility and Proper Administration
For off-label use in weight management, healthcare providers prescribe oral semaglutide to individuals with a body mass index (BMI) of 30 or higher. It may also be prescribed for those with a BMI of 27 or higher who have a weight-related health condition like high blood pressure. It is not intended for people with type 1 diabetes or those with a history of pancreatitis.
Proper administration is necessary for the medication to be effective. To ensure absorption, follow these steps:
- Take the tablet on an empty stomach immediately upon waking with no more than four ounces of plain water.
- Swallow the tablet whole, without crushing, splitting, or chewing it.
- Wait at least 30 minutes before eating, drinking anything other than plain water, or taking other oral medications.
- If a dose is missed, it should be skipped, and the regular schedule should resume the following day.