Why is oral semaglutide challenging to formulate?

Oral peptide medications face absorption barriers. Food intake, stomach acidity (gastric pH), and gastric emptying can all affect absorption, contributing to low bioavailability compared with injectable formulations.

How does oral semaglutide compare with injectable Wegovy® for weight loss results?

In STEP-1, once-weekly 2.4 mg injectable semaglutide produced an average 14.9% weight loss over 68 weeks. In the Phase 3 OASIS-4 trial, adults taking 25 mg oral semaglutide once daily achieved an average 13.6% weight loss over 64 weeks.

What is the FDA-labeled dosing schedule for Wegovy® tablets?

The labeled titration schedule is: Days 1–30: 1.5 mg once daily; Days 31–60: 4 mg once daily; Days 61–90: 9 mg once daily; Day 91 and onward (maintenance): 25 mg once daily.

How do you take oral semaglutide correctly for best absorption?

Take it once daily on an empty stomach in the morning with water only (up to 4 oz). Wait at least 30 minutes before eating, drinking anything else, or taking other oral medications. Swallow the tablet whole—do not crush, chew, or split.

Why isn’t Rybelsus® approved for weight loss?

Rybelsus® is oral semaglutide FDA-approved for type 2 diabetes, not for weight loss, and is available only up to 14 mg daily. Wegovy® tablets are FDA-approved for chronic weight management and follow a labeled titration schedule to a 25 mg once-daily maintenance dose.

Is compounded oral semaglutide the same as FDA-approved Wegovy® tablets?

No. Compounded oral semaglutide products are not interchangeable with FDA-approved Wegovy® tablets and may vary in formulation, dosing, stability, and absorption. Patients considering any non-brand oral semaglutide should review safety, dosing expectations, and cost with a prescribing clinician.

Do side effects differ between oral and injectable semaglutide?

No head-to-head clinical trials have directly compared oral versus injectable semaglutide, so firm statistical conclusions about differences cannot be made. Both forms share similar gastrointestinal side effects (nausea, diarrhea, vomiting, constipation, abdominal pain, decreased appetite) and share serious warnings including thyroid C-cell tumor risk, pancreatitis, gallbladder disease, acute kidney injury (often related to dehydration), and worsening diabetic retinopathy in certain populations.

Wegovy® Tablets (Oral Semaglutide) 25 mg: FDA Approval, Dosing, and What to Know

Q: What is oral semaglutide (Wegovy® tablets) and what changed in 2025?

Wegovy® tablets are FDA-approved oral semaglutide for chronic weight management in adults with obesity, or overweight with at least one weight-related condition. The approval also includes certain cardiovascular risk-reduction indications in adults with overweight or obesity and established cardiovascular disease.

Q: Who may qualify for FDA-approved oral semaglutide (Wegovy® tablets)?

Adults may qualify if they have obesity (BMI ≥30) or overweight (BMI ≥27) with at least one weight-related comorbidity, consistent with the FDA-labeled indication for weight management. Insurance coverage varies and typically depends on the FDA indication plus prior authorization requirements.

Joshua Silva, MD
Oct 30, 2025
5 min read

Updated: 3 days ago

What Is Oral Semaglutide and What Changed in 2025?

Update (January 2026): The FDA approved Wegovy tablets (oral semaglutide) on December 22, 2025 for chronic weight management in adults with obesity, or overweight with at least one weight-related condition. The approval also includes cardiovascular risk-reduction indications for certain adults with overweight or obesity and established cardiovascular disease.

In late 2025, oral semaglutide reached a major milestone with the FDA approval of Wegovy® tablets, making it the first oral GLP-1 receptor agonist specifically approved for chronic weight management. Prior to this, all FDA-approved GLP-1 medications for obesity required subcutaneous injection.

Wegovy® tablets offer a non-injectable weight-loss option while using the same active ingredient—semaglutide—as injectable Wegovy®. Unlike earlier oral semaglutide products approved only for type 2 diabetes, Wegovy® tablets follow a distinct FDA-labeled titration schedule designed to achieve therapeutic drug exposure for weight loss.

However, oral delivery of semaglutide presents unique challenges. Absorption is highly sensitive to stomach conditions, dosing requirements are more precise, and not all oral semaglutide products are equivalent. Understanding how FDA-approved oral semaglutide compares with injectable forms—and how it differs from compounded oral products—is essential before deciding whether it is the right treatment option.

Why Oral Semaglutide Is Challenging to Formulate

Oral peptides face absorption hurdles — food, gastric pH, and gastric emptying all impact absorption. Oral semaglutide is absorbed very poorly, leading to low bioavailability. Only 1% of Rybelsus® (the currently FDA-approved oral form for type 2 diabetes) actually reaches the bloodstream.

In contrast, the bioavailability of injectable semaglutide (Ozempic® & Wegovy®) is about 89%.

How Oral Semaglutide Compares With Injectable Wegovy® (Dose, Frequency, Results)

Semaglutide is a GLP-1 receptor agonist. Injected forms already approved for diabetes (Ozempic®) and obesity (Wegovy®) are given as once-weekly subcutaneous injections.

To improve absorption, oral semaglutide is formulated with an absorption enhancer (SNAC), allowing it to cross the stomach lining more efficiently and enter the bloodstream.

The STEP-1 clinical trial showed that once-weekly 2.4 mg injectable semaglutide produced an average 14.9% weight loss over 68 weeks.
In the Phase 3 OASIS-4 trial, adults taking 25 mg oral semaglutide daily achieved an average 13.6% weight loss over 64 weeks.

	Step 1 Trial	OASIS 4 Trial
Medication	Semaglutide	Semaglutdie
Method of Administration	Subcutaneous Injection	Oral Tablet
Dose	2.4 mg	25 mg
Frequency	Once Weekly	Once Daily
Duration	68 weeks	64 weeks
Percent Weight Loss	14.9%	13.6%

Wegovy® Tablets Dosing Schedule (FDA label)

The FDA-labeled titration schedule for Wegovy® tablets is:

Days 1–30: 1.5 mg once daily
Days 31–60: 4 mg once daily
Days 61–90: 9 mg once daily
Day 91 and onward (maintenance): 25 mg once daily

How to take oral semaglutide correctly

For best absorption, the label instructs patients to:

Take once daily on an empty stomach in the morning with water only (up to 4 oz)
Wait at least 30 minutes before eating, drinking anything else, or taking other oral medications
Swallow the tablet whole (don’t crush/chew/split)

Why Rybelsus® Is Not Approved for Weight Loss

Rybelsus® is oral semaglutide FDA-approved for type 2 diabetes, not for weight loss. Wegovy® tablets are specifically FDA-approved for chronic weight management (and certain cardiovascular risk-reduction indications), with a labeled titration schedule reaching a 25 mg once-daily maintenance dose, whereas Rybelsus® is only available up to 14 mg daily.

Compounded Oral Semaglutide vs FDA-Approved Wegovy

You may see compounded oral semaglutide offered by various online distributors. However, these products are not interchangeable with FDA-approved oral semaglutide tablets, and the dosing and formulation often differ substantially.

Many compounded oral options are offered at low or variable doses that are unlikely to achieve the exposure associated with meaningful weight loss. For example, some sites list oral capsules in the 3 mg, 6 mg, or 9 mg range, while others sell liquid formulations with concentrations such as 1.25–7.5 mg per mL in multi-milliliter vials. When attempting to reach doses comparable to those studied in clinical trials (25 mg per day), providing sufficient compounded medication can quickly become cost-prohibitive.

Now that Wegovy tablets are FDA-approved, it’s important for patients to understand that “oral semaglutide” is not a single, standardized product. The FDA-approved tablet formulation is specifically engineered for absorption and follows a clearly defined, evidence-based titration schedule that progresses to a 25 mg once-daily maintenance dose.

By contrast, compounded oral semaglutide products may vary widely in formulation, dosing, stability, and absorption, and they may not produce the same drug exposure or clinical results observed in FDA-reviewed trials. For patients considering any non-brand oral semaglutide, a discussion with a prescribing clinician is essential to review safety, dosing expectations, cost considerations, and whether an FDA-approved option is appropriate.

How Do Side Effects Compare Between Oral and Injectable Semaglutide?

No head-to-head clinical trials have directly compared oral versus injectable semaglutide, so no firm statistical conclusions can be made regarding differences in effectiveness or tolerability.

Both forms share a similar gastrointestinal side-effect profile, including nausea, diarrhea, vomiting, constipation, abdominal pain, and decreased appetite.

Serious risks and warnings are also shared, including a boxed warning for thyroid C-cell tumors, as well as risks of pancreatitis, gallbladder disease, acute kidney injury (often related to dehydration), and worsening diabetic retinopathy in certain populations.

Who May Qualify for FDA-Approved Oral Semaglutide (Wegovy® Tablets)?

Adults may qualify if they have obesity (BMI ≥30), or overweight (BMI ≥27) with at least one weight-related comorbidity, consistent with the FDA-labeled indication for weight management. Coverage still varies by plan and usually depends on the FDA indication plus prior authorization requirements.

While oral semaglutide expands access for patients who prefer non-injectable options, medication choice should be individualized based on effectiveness, tolerability, cost, and long-term weight-maintenance goals.

Disclaimer: This article is for educational purposes only and is not a substitute for professional medical advice.

About the Author

Dr. Joshua Silva, MD, is a licensed physician and Medical Director of Potere Health MD. After graduating medical school from the University of Hawaii, he completed residency training in Occupational and Environmental Medicine from the University of Utah where he also earned a master's degree in Occupation Health. He now specializes in evidence-based weight management, including GLP-1/GIP therapies (semaglutide & tirzepatide). Dr. Silva provides in-person and virtual care for patients with clinics in Salt Lake City, St. George, and Cedar City, Utah.

Sources:

Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). New England Journal of Medicine. 2021;384:989-1002. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa2032183
OASIS-4 Investigators. Oral Semaglutide 25 mg for Weight Management in Adults with Overweight or Obesity. New England Journal of Medicine. 2025. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa2500969
FDA Clinical Pharmacology Review for Oral Semaglutide (Rybelsus). NDA 213051. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/213051Orig1s000ClinPharmR.pdf
Granhall C, et al. Oral Semaglutide: A Review of the First Oral GLP-1 Receptor Agonist. Diabetes Ther.2020;11(6):1347-1362. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC7364672/
FDA Prescribing Information (Rybelsus®). 2024 update. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/213051s018lbl.pdf
FDA Prescribing Information (Wegovy®). 2025 update. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/218316Orig1s000lbl.pdf
U.S. Food and Drug Administration (FDA). FDA has approved a new oral form of semaglutide for long-term weight reduction… (Facebook post). Available at:
https://www.facebook.com/FDA/posts/fda-has-approved-a-new-oral-form-of-semaglutide-for-long-term-weight-reduction-i/1259166499574039/
U.S. Food and Drug Administration (FDA). FDA’s concerns with unapproved GLP-1 drugs used for weight loss.Available at:
https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss