Since the FDA ended the semaglutide shortage in February 2025, compounders have pivoted to "significantly different" formulations to stay legal. Sublingual drops—liquid medication held under the tongue—are one of the most popular alternatives. But do they actually work as well as injections?
The short answer: probably not. Here's what the science and FDA say about sublingual semaglutide, and why the needle-free promise may come with significant tradeoffs.
Why Sublingual Semaglutide Exists
To understand sublingual semaglutide, you need to understand the regulatory shift that created it.
When the FDA declared GLP-1 shortages resolved, pharmacies could no longer legally compound "essential copies"—simple injectable semaglutide that's basically identical to Wegovy or Ozempic. The only remaining legal pathway is to create formulations with a "significant difference" from the brand-name product.
Sublingual delivery counts as a significant difference because:
- • It's a different route of administration (under the tongue vs. injection)
- • No FDA-approved sublingual semaglutide exists
- • The formulation requires different inactive ingredients
So sublingual semaglutide exists primarily because of a legal workaround—not because science shows it's an effective way to deliver the medication.
The Bioavailability Problem
The fundamental challenge with sublingual semaglutide is bioavailability—how much of the drug actually gets into your bloodstream where it can work.
Bioavailability by Delivery Method
*No published clinical data; estimate based on similar peptides
Why Peptides Don't Absorb Well Orally
Semaglutide is a large peptide molecule—essentially a small protein. Large molecules face significant barriers to absorption through mucous membranes like the mouth:
- 1. Size matters: Semaglutide has a molecular weight of about 4,114 Da. Drugs that absorb well sublingually are typically under 500 Da.
- 2. Enzymatic degradation: Saliva contains enzymes that can break down peptides before they absorb.
- 3. Limited surface area: The sublingual membrane is small compared to the GI tract.
Novo Nordisk had to develop special absorption-enhancing technology for Rybelsus (oral semaglutide tablets), and even then, bioavailability is only about 1%—requiring much higher doses to achieve therapeutic effects. They haven't developed a sublingual version, likely because the science doesn't support it.
What the FDA Says
The FDA has been explicit about its concerns with alternative delivery forms of compounded GLP-1s:
FDA Warning (2025)
The FDA warns that sublingual, troche, nasal spray, and other non-injectable forms of compounded semaglutide "have not been reviewed for safety or efficacy" and "have not been shown to be safe and effective." The agency specifically notes that potency testing of these products found variations ranging from 42% to 170% of the labeled strength.
This isn't just bureaucratic caution. The FDA is pointing out that:
- • No clinical trials have studied sublingual semaglutide
- • We don't know what dose actually reaches the bloodstream
- • Quality control testing shows major potency problems
- • Side effects and safety profile are unknown for this delivery method
Head-to-Head Comparison
| Factor | Injectable | Sublingual |
|---|---|---|
| Bioavailability | ~89% (proven) | Unknown (likely low) |
| Clinical trial data | Extensive (STEP trials) | None |
| FDA review | Approved as Wegovy/Ozempic | Not reviewed |
| Potency consistency | Varies by compounder | 42-170% variation (FDA testing) |
| Dosing precision | Requires calculation | Requires calculation |
| Needle-free | No | Yes |
| Legal pathway (post-shortage) | Only with additives | Yes (significant difference) |
Real-World Reports
Patient experiences with sublingual semaglutide are mixed. Common patterns from online forums and reviews include:
Positive reports:
- • Some users report appetite suppression and weight loss
- • Fewer GI side effects in some cases (possibly due to lower absorption)
- • Convenience of no needles
Negative reports:
- • Slower or minimal results compared to injectable
- • Questions about whether it's actually working
- • Unpleasant taste
- • Inconsistent effects batch-to-batch
Important Context
Some positive reports may reflect the placebo effect, which is significant in weight loss studies. Others may reflect that some medication is being absorbed—just potentially less than with injections. Without controlled studies, it's impossible to know.
The Appeal: Why People Choose Sublingual
Despite the scientific concerns, sublingual semaglutide remains popular for understandable reasons:
Our Recommendation
Based on available evidence, here's how we'd rank your options:
Best: FDA-approved injectable (Wegovy, Zepbound)
Proven efficacy, quality guaranteed, pre-filled pens eliminate dosing errors
Good: Compounded injectable (with additives)
Same delivery method as proven products, absorption is predictable
Uncertain: Sublingual drops
No clinical data, unknown bioavailability, significant potency variation
If needle fear is your primary concern, consider that many people who were initially afraid of injections find the reality is much easier than expected—the needles are tiny and the injection is once weekly. Working with a provider who offers injection training may help you overcome this barrier and access a more proven delivery method.
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