Oral GLP-1s: Four Products, Two Chemistries, One Label That Says They Are Not Interchangeable

There are now four oral GLP-1 products with a current US label, and the most useful thing to know about them is that they are not variations on one idea. They are two entirely different solutions to the same problem, and the problem is that the gut digests peptides.

This page is the register: which products exist, what each one's label says about how it is absorbed and how it is taken, and where the two chemistries diverge. The absorption mathematics of oral versus injected dosing is on our comparison of the pill and the injection, and the priced, trial-by-trial account of the two weight-loss tablets is on what the GLP-1 pills cost and what they do. What follows is neither. It is the category.

The register, read from the labels on 2026-09-19

Two things about that table are worth stating plainly, because the brand names hide them.

Four products, two molecules. Three of the four are semaglutide. The oral category is not four competing drugs; it is one peptide sold in three formulations and one small molecule sold in one.

Two of the four are recent additions to brand names that used to mean an injection. One Novo Nordisk label document covers Ozempic tablets and Rybelsus tablets together; another covers the Wegovy injection and Wegovy tablets together. A person who says "I'm on Ozempic" in 2026 has not said whether they inject it.

Rybelsus's withdrawal is the one moving part. FDA's shortage database carries a 2026-06-04 notice for all three strengths stating that they will be replaced by Ozempic tablets, which we covered when writing about what is replacing compounded semaglutide. On the record available it reads as a renaming and a change of strengths inside one application rather than a withdrawal on safety grounds.

Strategy one: carry the peptide past the stomach

Semaglutide is a peptide of 4,113.58 g/mol whose backbone is produced by yeast fermentation. Swallowed on its own, essentially none of it would survive.

All three semaglutide tablets are therefore co-formulated with salcaprozate sodium, which the labels abbreviate to SNAC and describe as an absorption enhancer. The labels are specific about where it works: "the absorption of semaglutide predominantly occurs in the stomach."

The measured result is small and the labels do not soften it:

• RYBELSUS: 0.4% to 1% absolute bioavailability across 3, 7 and 14 mg.
• OZEMPIC tablets: 1% to 2% across 1.5, 4 and 9 mg.
• WEGOVY tablets: approximately 1% to 2%.

Maximum concentration is reached about one hour after the dose in all three.

The excipient list is the whole difference between two of them

The Rybelsus and Ozempic tablet ladders are engineered to land in the same place. The label states there were no clinically significant differences in steady-state AUC or Cmax between 3, 7 and 14 mg of Rybelsus and 1.5, 4 and 9 mg of Ozempic tablets, measured in healthy subjects. Those are milligram ratios of 2.00, 1.75 and 1.56 — the Ozempic formulation reaching the same exposure from between a half and two-thirds of the drug.

What differs is the tablet around the semaglutide, and the label prints both lists:

• RYBELSUS: magnesium stearate, microcrystalline cellulose, povidone, SNAC.
• OZEMPIC tablets: magnesium stearate, SNAC.

Two excipients against four. A tablet with less in it delivering more of what it contains is why the label opens by warning that the two are not substitutable on a mg-to-mg basis — the first bullet of its Dosage and Administration section, ahead of anything about food or water.

The four conditions attached to every semaglutide tablet

Getting 1% of a peptide across the stomach lining requires the stomach to be in a particular state, and all three labels impose the same conditions:

1. Once daily, on an empty stomach, in the morning.
2. Water only, and no more than 4 ounces of it.
3. Swallowed whole — not split, crushed, chewed or dissolved.
4. Then at least 30 minutes before any food, any other drink, or any other oral medicine.

That is a set of instructions from a regulator-approved label, reported here as a record of what the label requires. It is not guidance from us, and the question of whether any of these products is appropriate for a particular person belongs with a prescriber.

Strategy two: use a molecule that is not a peptide

Orforglipron, sold as Foundayo, activates the same receptor without being a peptide. Its label gives a molecular weight of 902.0 g/mol for orforglipron calcium — about a 4.6-fold difference from semaglutide — and describes it as "a white to practically white to light brown solid that is hygroscopic," and as insoluble in water.

A molecule insoluble in water that is 77% orally bioavailable is the counterintuitive part, and it is what the different chemistry buys. From the label:

• Absolute bioavailability 77% (geometric mean, after a 0.8 mg dose).
• Maximum concentration at 4 to 8 hours, against about 1 hour for the semaglutide tablets.
• No clinically relevant food effect. In a study of an investigational 37.5 mg tablet, food reduced AUC over 24 hours by 19% and Cmax by 26%, with tmax and half-life unchanged.
• Elimination half-life approximately 29 to 49 hours after an oral dose; plasma protein binding above 99%; mean steady-state volume of distribution about 285 L; mean systemic clearance 7.15 L/hour.

And so the administration section is three lines rather than four conditions: once daily, with or without food, swallowed whole, no more than one tablet a day.

What the two strategies cost in discarded drug

Here is the arithmetic the labels support, at each product's maximum labelled dose:

This is a comparison of formulations, not of strengths. The two molecules are not equipotent, no trial has compared them, and a milligram of one is not a milligram of the other. What the table does show is that the peptide route works by manufacturing and shipping between fifty and two hundred and fifty times more drug than any patient absorbs, and that the non-peptide route does not. That is a fact about supply chains and cost structure as much as about pharmacology, and it is the reason a second oral chemistry was worth a decade of pursuit.

The escalation the oral route requires

Because so little of a semaglutide tablet is absorbed, the maintenance dose is large in milligram terms, and the climb to it is the longest in the class.

Foundayo's fold increase is the largest of the four and its steps are the label's longest, so the two chemistries do not divide neatly into "oral means a long titration." What does divide neatly is the reason each label gives for escalating at all, which in every case is gastrointestinal tolerability rather than efficacy. The published schedules for the whole class, side by side, are on our page of the approved GLP-1 titration schedules.

One brand, two routes, and a label that tells you how to cross

Because the Wegovy label now covers both a pen and a tablet, it is the only GLP-1 document that sets out switching between an injection and a tablet of the same molecule. It does so in both directions: from the 2.4 mg injection to 25 mg tablets one week after the last injection, and from 25 mg tablets to the injection the day after the last tablet. It also provides for someone who cannot tolerate the 25 mg tablet to move to the 1.7 mg injection.

Those are the label's provisions, recorded here because no other product in the class has them.

The advantage nobody advertises

Every GLP-1 injection pen sold in the United States is refrigerated between 2°C and 8°C until first use, with a limited window out of the fridge afterwards — 28 days for a Wegovy single-dose pen or syringe, 56 days for the multi-dose FlexTouch pen.

All four tablets are stored at 20°C to 25°C, ordinary controlled room temperature, excursions permitted from 15°C to 30°C.

For anyone travelling, anyone whose electricity supply is unreliable, and anyone without a fridge they control, that is the clearest categorical difference between an oral GLP-1 and an injected one, and it appears in the labels rather than in the advertising.

What is not established

• No head-to-head trial exists between any two oral GLP-1s, and none exists between an oral GLP-1 and an injected one for weight loss.
• The labels compare formulations only within a molecule. The Rybelsus-to-Ozempic-tablet exposure comparison was run in healthy subjects, not in patients with obesity or type 2 diabetes, and the Wegovy label separately notes that lower semaglutide blood concentrations after the tablets in patients with type 2 diabetes "may be associated with reductions in absolute bioavailability."
• Bioavailability is not effectiveness. How much of a tablet is absorbed says nothing on its own about how much weight anyone loses; those results are per-product and are in each label's clinical studies section.

Sources

Every figure on this page was read on 2026-09-19 from these documents:

• OZEMPIC and RYBELSUS tablets, prescribing information — DailyMed set id 27f15fac-7d98-4114-a2ec-92494a91da98, version 14, published 2026-08-19.
• WEGOVY injection and WEGOVY tablets, prescribing information — set id ee06186f-2aa3-4990-a760-757579d8f77b, version 19, published 2026-06-30.
• FOUNDAYO (orforglipron) tablets, prescribing information — set id 8ac446c5-feba-474f-a103-23facb9b5c62, version 10, published 2026-08-13.
• ZEPBOUND (tirzepatide) prescribing information via openFDA, label effective 2026-08-28.