Metabolic / Published Sep 8, 2026 / Reviewed Sep 27, 2026 / 10 min read
Oral GLP-1s in 2026: Wegovy Pill vs Foundayo (Orforglipron) vs Rybelsus, and What Is Coming
Written by Aaron CuhaReviewed Sep 27, 2026
The three approved GLP-1 pills, why one needs an empty stomach and another doesn't, how much weight people lost in the studies behind each approval, the warning box they all carry, and what's coming: aleniglipron, elecoglipron, HRS-7535, and the pill Pfizer walked away from. Plain English.
Key takeaways
- The FDA has approved three GLP-1 pills. Rybelsus (semaglutide pill) for type 2 diabetes, on September 20, 2019. The Wegovy pill (semaglutide 25 mg) for weight and heart risk, on December 22, 2025. Foundayo (orforglipron) for weight, on April 1, 2026.
- Semaglutide is a peptide. It only survives the stomach thanks to an added ingredient called SNAC, and only if you take it on an empty stomach with up to 4 ounces of water, then wait 30 minutes. Orforglipron is a small-molecule drug, not a peptide, and you can take it with or without food.
- In 3,127 people over 72 weeks, orforglipron 36 mg took off 11.2% of body weight, or 12.4% for people who kept taking it. In 307 people over 64 weeks, the semaglutide 25 mg pill took off 13.6%, or 16.6% for people who kept taking it.
- Both weight-loss pills carry the same boxed warning about thyroid tumors. People with a personal or family history of a rare thyroid cancer (medullary thyroid carcinoma) or MEN 2 should not take them. That holds even for orforglipron, which does not work in rodents and did not cause the tumors.
- Coming next: HRS-7535 (about 10% to 11% at 44 to 50 weeks in big studies in China, sent for approval there), elecoglipron (up to 10.5% in a 36-week study, big studies announced) and aleniglipron (16.3% more than a dummy pill at 44 weeks, big studies starting late 2026). Pfizer dropped danuglipron in April 2025 after one person had liver injury.
Which GLP-1 pills are approved in 2026?
Direct answer
Three in the US as of September 2026. Rybelsus, a semaglutide pill for type 2 diabetes, approved September 20, 2019. The Wegovy pill, semaglutide 25 mg for weight and lowering heart risk, approved December 22, 2025. Foundayo, orforglipron, the first small-molecule GLP-1 pill for weight, approved April 1, 2026. Everything else is still being tested.
Until December 2025, the only GLP-1 you could swallow was a diabetes drug, and it came with fasting rules. Two approvals in four months changed that. They are two different kinds of chemistry with different rules. This article pulls them apart, puts every study number next to its study and length, and lists what is coming next. Profiles: semaglutide, orforglipron.
Why does a peptide pill need an empty stomach and a small molecule does not?
Direct answer
Semaglutide is a peptide, and stomach enzymes would normally digest it. The pill is mixed with SNAC, a salt that helps the peptide pass through the stomach wall. That only works when the stomach is empty. So the label says: empty stomach, up to 4 ounces of water, wait 30 minutes. Orforglipron is a small-molecule drug, not a peptide, and you can take it with or without food.
How SNAC works was figured out in 2018. The pill dissolves against the stomach wall. SNAC holds back the acid and helps the peptide get through the stomach lining, so it is absorbed in the stomach, not the gut (Buckley et al., 2018). It is clever but fragile. Food, other drinks or other pills taken at the same time get in the way. That is why the Wegovy pill label says once a day in the morning, on an empty stomach, with up to 4 ounces of water, swallowed whole, and at least 30 minutes before eating, drinking anything else or taking other pills (FDA label, Wegovy tablets, December 2025). Orforglipron was built from the start as a small molecule that works on the GLP-1 signal without being a peptide. Its label says once a day, with or without food (FDA label, Foundayo, April 2026). That one line is most of Foundayo's practical selling point.
What did the studies behind each approval show?
Direct answer
ATTAIN-1, 3,127 people over 72 weeks: orforglipron 36 mg took off 11.2% of body weight, against 2.1% on a dummy pill. PIONEER 1, 703 people over 26 weeks: semaglutide 14 mg lowered long-term blood sugar (HbA1c) by 1.1 points. OASIS 4, 307 people over 64 weeks: semaglutide 25 mg took off 13.6%, against 2.2% on a dummy pill.
| Drug | What kind | Study | Who | How long | What happened | Quit because of side effects | Size of the evidence |
|---|---|---|---|---|---|---|---|
| Foundayo (orforglipron 36 mg) | Small molecule | ATTAIN-1 (NEJM, September 2025) | 3,127 adults with obesity, no diabetes | 72 weeks | 11.2% weight loss against 2.1% on a dummy pill, counting everyone who started; 12.4% against 0.9% for people who kept taking it; 18.4% lost 20% or more | 10.3% on 36 mg, against 2.7% on the dummy pill | Large final-stage study in people |
| Rybelsus (semaglutide pill 14 mg) | Peptide plus SNAC | PIONEER 1 (Diabetes Care, 2019) | 703 adults with type 2 diabetes | 26 weeks | Long-term blood sugar (HbA1c) down 1.1 points more than the dummy pill; weight down 2.3 kg | 2.3% to 7.4%, against 2.2% | Large final-stage study in people |
| Wegovy pill (semaglutide pill 25 mg) | Peptide plus SNAC | OASIS 4 (NEJM, September 2025) | 307 adults with overweight or obesity, no diabetes | 64 weeks | 13.6% weight loss against 2.2% on a dummy pill, counting everyone who started; 16.6% against 2.7% for people who kept taking it; 34.4% lost 20% or more | Not given in the summary; stomach problems in 74.0%, against 42.2% | Large final-stage study in people |
Two warnings when you read the table. The semaglutide pill and orforglipron numbers come from different studies, of different lengths, in different people. The only fair thing to say is that in its own study, the semaglutide pill took off more weight than orforglipron did in its study (NEJM, OASIS 4; NEJM, ATTAIN-1). Also, Foundayo pills are labeled 0.8 to 17.2 mg, while the ATTAIN-1 paper reports 6, 12 and 36 mg. So the numbers on the box won't match the numbers in the paper. Rybelsus was approved on ten PIONEER studies in 9,543 people, and it is still a diabetes drug only (Diabetes Care, PIONEER 1).
What is the boxed warning on the GLP-1 pills?
Direct answer
A risk of tumors in the thyroid's C-cells. Semaglutide causes these tumors in rats and mice. Whether it does in people is unknown. Orforglipron does not work in rodents and did not cause the tumors, but its label carries the same warning for the whole drug family. People with a personal or family history of medullary thyroid cancer or MEN 2 should not take either.
The Foundayo warning box is unusual. It says plainly that the drug did not cause the tumors in rodents, then applies the warning anyway, because it acts on the human GLP-1 signal. Beyond the box, both labels list swelling of the pancreas, gallbladder problems, sudden kidney damage from losing fluids, severe stomach problems, low blood sugar when taken with insulin or sulfonylureas, and breathing food into the lungs during surgery. Foundayo adds that some other drugs raise its levels (a top dose of 9 mg with strong CYP3A4 blockers). It also slows stomach emptying enough to affect other pills. In ATTAIN-1, nausea hit 33.7% on 36 mg against 10.4% on the dummy pill, and vomiting 24.0% against 3.5% (Eli Lilly, April 2026). Pills don't escape this drug family's gut side effects. They only change how you take the drug.
Which oral GLP-1s are coming next?
Direct answer
Three small-molecule pills have big final-stage studies planned or done. HRS-7535 took off 10.9% at 44 weeks in two big studies in China in July 2026. Elecoglipron took off up to 10.5%, against 0.6% on a dummy pill, in a 36-week study of 310 people. Aleniglipron took off 16.3% more than a dummy pill at 44 weeks on 180 mg, in 85 people (ACCESS II, March 2026).
| Compound | Company | Best result | Where it stands | Size of the evidence |
|---|---|---|---|---|
| HRS-7535 | Hengrui and Kailera | 9.5% and 10.9% at 44 weeks on 120 and 180 mg, against 2.5% (HARBOR-1, 556 people in China, for people who kept taking it); 11.1% at week 50 | Sent for approval in China; worldwide study started April 2026, results 2027 | Large final-stage studies in people (China) |
| Elecoglipron | AstraZeneca | 2.6% to 10.5%, against 0.6% on a dummy pill, across 5 to 75 mg (VISTA, 310 people, 36 weeks) | Big final-stage studies announced 2026 | Mid-sized study in people |
| Aleniglipron | Structure Therapeutics | 14.7%, 16.3% and 16.0% more than a dummy pill at 44 weeks on 120, 180 and 240 mg (ACCESS II, 85 people); still losing | Met with the FDA in spring 2026; big studies planned for the second half of 2026 | Mid-sized study in people |
| Danuglipron | Pfizer | Twice-a-day version dropped because people felt too sick; once-a-day dose-finding study finished | Dropped April 14, 2025 | Studies in people, then dropped |
Aleniglipron's number is how much more weight people lost than on a dummy pill. That usually runs 2 to 3 points lower than the plain averages used for the approved drugs. Even so, it beats orforglipron's 72-week result in less time (Structure Therapeutics, March 2026). Elecoglipron's VISTA results were published in the Lancet in 2026 (Lancet, VISTA). In HRS-7535's studies in China, 3.1% to 4.1% quit because of side effects, against 2.7% on a dummy pill, and there were no signs of liver trouble (Kailera, July 2026). That last point matters because of danuglipron.
What happened to danuglipron?
Direct answer
Pfizer dropped it on April 14, 2025. Its once-a-day version had hit its targets for how the body handles it. But one person in a dose-finding study, with no symptoms, showed possible liver injury from the drug, which cleared up after stopping. Liver test rises across more than 1,400 people were in line with similar drugs. Pfizer and regulators still judged the one case enough to stop.
Danuglipron is a reminder that small-molecule GLP-1 pills are new chemistry. Peptides like semaglutide break down into protein building blocks. A lab-made small molecule is broken down by the liver, so liver safety has to be proven drug by drug (Pfizer, April 2025). Orforglipron's 3,127-person study and the HRS-7535 studies in China showed no such problem. Pfizer replaced danuglipron by buying Metsera and its weight-loss shot berobenatide. For the shots, see the 2026 GLP-1 field guide.
The bottom line
In 2026, the choice between GLP-1 pills comes down to two things. One is a peptide that did better in its study but needs a fasting routine. The other is a small molecule that fits a normal morning but took off less weight in its study. Both fall well short of the shots. The next wave, led by aleniglipron, may close that gap. Liver safety will be watched drug by drug because of what happened to danuglipron.
Frequently asked questions
Is there a GLP-1 pill for weight loss?
Yes, two as of 2026: the Wegovy pill (semaglutide 25 mg, approved December 22, 2025) and Foundayo (orforglipron, approved April 1, 2026). Rybelsus is approved only for type 2 diabetes.
Which is better, the Wegovy pill or Foundayo?
Nobody has tested them against each other. In their own studies, the semaglutide pill took off 13.6% of body weight at 64 weeks (OASIS 4) and orforglipron 11.2% at 72 weeks (ATTAIN-1). You can take Foundayo with food. You can't with the Wegovy pill.
Do GLP-1 pills work as well as injections?
Not in the studies so far. The semaglutide 25 mg pill's 13.6% and orforglipron's 11.2% fall below tirzepatide's 20.9% (SURMOUNT-1, 72 weeks) and retatrutide's 28.3% (TRIUMPH-1, 80 weeks).
Why was danuglipron discontinued?
Pfizer stopped it in April 2025 after one person in a dose-finding study showed possible liver injury from the drug. It cleared up after they stopped taking it.
Compound profiles mentioned
- SemaglutideStrong. At least two finished studies in people, and at least 1,000 people who took it. 12 completed trials, 42,363 people given it.Metabolic
- OrforglipronStrong. At least two finished studies in people, and at least 1,000 people who took it. 8 completed trials, 17,383 people given it.Metabolic
- AleniglipronLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.Metabolic
- ElecoglipronLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, none stating how many people.Metabolic
- HRS-7535Moderate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 235 people given it.Metabolic
- DanuglipronLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.Metabolic
- TirzepatideStrong. At least two finished studies in people, and at least 1,000 people who took it. 9 completed trials, 22,802 people given it.Metabolic
- RetatrutideStrong. At least two finished studies in people, and at least 1,000 people who took it. 5 completed trials, 1,345 people given it.Metabolic
- BerobenatideLimited. People have taken it in a published study, but fewer than 100 of them. 3 completed trials, none stating how many people.Metabolic
Sources
- Study in people2025
Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment (ATTAIN-1)
3,127 people: 11.2% weight loss on 36 mg, against 2.1% on a dummy pill at 72 weeks. 10.3% quit because of side effects.
New England Journal of Medicine - Study in people2025
Oral semaglutide at a dose of 25 mg in adults with overweight or obesity (OASIS 4)
307 people: 13.6% weight loss, against 2.2% on a dummy pill at 64 weeks, counting everyone who started. Stomach problems in 74.0%, against 42.2%.
New England Journal of Medicine - Study in people2026
Elecoglipron, an oral small molecule GLP-1 receptor agonist in adults with obesity or overweight (VISTA): a multicentre, phase 2, randomised, placebo-controlled clinical trial
310 people: 2.6% to 10.5% weight loss, against 0.6% on a dummy pill over 36 weeks.
The Lancet - Study in people2026
Structure Therapeutics reports 44-week topline data from Phase 2 ACCESS II trial with aleniglipron
85 people: 16.3% more weight loss than a dummy pill at 44 weeks on 180 mg. Big studies planned for the second half of 2026.
Structure Therapeutics (SEC filing) - Study in people2025
FDA approves Novo Nordisk's Wegovy pill, the first and only oral GLP-1 for weight loss in adults
Approved December 22, 2025 for weight and lowering heart risk. 16.6% for people who kept taking it in OASIS 4.
Novo Nordisk company announcement - Study in people2026
FDA approves Lilly's Foundayo (orforglipron), the only GLP-1 pill for weight loss that can be taken any time of day without food or water restrictions
Approved April 1, 2026. No food or water rules. Boxed warning for thyroid tumors.
Eli Lilly press release - Study in people2026
Foundayo (orforglipron) tablets, prescribing information
Boxed warning for thyroid C-cell tumors. Pills from 0.8 to 17.2 mg, with or without food.
FDA - Study in people2025
Pfizer provides update on oral GLP-1 receptor agonist danuglipron
Dropped April 14, 2025 after one case of possible liver injury from the drug.
Pfizer press release - Animal study2018
Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist
In animals, SNAC let semaglutide pass through the stomach lining.
Science Translational Medicine
Read next
- Retatrutide vs Tirzepatide vs Semaglutide vs the Pill: The 2026 GLP-1 Field Guide
- FDA Peptide Status in 2026: The Category 2 Removals, the July Votes, and What Actually Changed
- New Peptides and Longevity Compounds in 2026: What Is Actually New, What Is Newly Legal, and What Is Just New to Vendors
- How to Read a Peptide Certificate of Analysis: HPLC Purity, Mass Spec Identity, Endotoxin, and Janoshik Verification
Educational use only. This database summarizes published research and is not medical advice. Where a dose appears it is a record of what a trial or clinic ran, or what people describe doing, with its source attached. Nothing here is a recommendation for personal use. Sellers named on the price pages are ranked by certificate tier, then price, and any affiliate income is disclosed there. Naming a seller is not a recommendation to buy or use anything.