GLP-1 pill or shot? What the trials show

The four products at a glance

All four switch on the GLP-1 receptor, the gut-hormone target behind this whole class of medicines. Zepbound also switches on a second receptor, GIP. Wegovy, in both forms, contains semaglutide, a peptide. Foundayo contains orforglipron, a small molecule that is not a peptide. The semaglutide, orforglipron and tirzepatide pages have the details on each medicine.

Uses, timing rules and warnings are from the prescribing information the Atlas read (Wegovy 5/2026, Foundayo 7/2026, Zepbound 4/2026). The Wegovy pill label covers adults only. Labels change, so check the current label. The Atlas gives no conversion between the strengths of any of these products.

What the main trials found

Each product has a large placebo-controlled trial behind its weight-management label. The table lists one for each, with the dose that produced the biggest average change. None of the four trials enrolled people with diabetes.

The gap is the placebo average subtracted from the medicine average. For OASIS 4 and STEP 1 it is the estimated difference the papers report (11.4 and 12.4 points). For ATTAIN-1 and SURMOUNT-1 the Atlas subtracted the two reported averages. ATTAIN-1, STEP 1 and SURMOUNT-1 report effects regardless of whether people stayed on treatment. The OASIS 4 abstract does not name its analysis. The trial results explorer shows weight-loss trials in your own pounds. Foundayo's label reports the ATTAIN-1 result under the marketed strengths, with -11.1% for the highest strength and -2.1% on placebo at week 72. Novo Nordisk funded OASIS 4 and STEP 1. Eli Lilly funded ATTAIN-1 and SURMOUNT-1.

Why the table is not a scoreboard

The four trials ran separately, in different years, with different people. A bigger number in one row does not prove that product works better, because the rows differ in ways that move the average.

OASIS 4 was a smaller trial than the other three: 205 adults took the pill and 102 took placebo. The other trials enrolled between 1,961 and 3,127 people. A small trial gives a less precise average, which is why OASIS 4's confidence interval for the gap (9.0 to 13.9 points) is wide compared with STEP 1's (11.5 to 13.4).

The lengths differ, from 64 to 72 weeks, and so do the dose steps people climbed on the way. The Foundayo trial used tablet strengths that carry different names from the ones now sold, so the label reports the same trial under the marketed names with slightly different numbers.

• Different people: each trial set its own entry rules, and averages shift with the starting weight and mix of participants.
• Different analyses: a count of everyone randomized gives a smaller average than a count of people while they were taking the drug (see the next section).
• Different makers: each company ran its own trial of its own product, and none of the four is a head-to-head.

Why a company's headline number can be larger

An estimand is the exact question a trial's analysis answers. One version counts everyone randomized, including people who stopped the medicine or needed other treatment. Another counts results only while people were still taking the medicine. The second version gives bigger averages, and companies often lead with it.

For OASIS 4, a trade-press report cites 16.6% for the pill against 2.7% for placebo on the while-taking version, compared with the 13.6% and 2.2% in the paper's abstract. Eli Lilly's headline figure for Foundayo's highest dose is likewise larger than the paper's 11.2%, because it counts only people while they were taking the drug. The table above sticks to the numbers from the published abstracts. When you see a pill or injection number somewhere else, check which version it is before lining it up against another.

Has any trial compared a pill with an injection?

Not in adults with obesity, as far as the Atlas found. A search of ClinicalTrials.gov for orforglipron, and for oral semaglutide in obesity and overweight, turned up placebo-controlled trials and maintenance trials, but no registered trial that randomizes people with obesity to a pill or an injection. Pill-versus-injection trials do exist in type 2 diabetes, such as orforglipron against dulaglutide or insulin glargine. They test blood sugar control, not weight-loss labels.

The nearest trials answer different questions. SURMOUNT-5 compared two injections, tirzepatide and semaglutide, and found an average change of -20.2% against -13.7% at 72 weeks. It was open label and Eli Lilly paid for it. ATTAIN-MAINTAIN gave the pill orforglipron to adults who had finished a year of weekly tirzepatide or semaglutide injections. Those on the pill kept more of their weight reduction over the next 52 weeks than those on placebo, but nobody stayed on the injection, so it cannot show how the pill compares with continuing the shot. The weight regain after stopping page has the numbers.

How do the side effects compare?

The label tables for the Wegovy injection, Foundayo and Zepbound list the same kinds of effects, mostly digestive, and all three include nausea, vomiting, diarrhea, constipation and abdominal pain. The Wegovy pill label has no table of its own for these. It says the types and frequency of common reactions in its pill trial were similar to those in the injection table. In OASIS 4, any digestive adverse event was reported by 74.0% on the pill and 42.2% on placebo.

Each cell is the column for the highest strength in that label's table. Wegovy's table pools three trials of up to 68 weeks. Foundayo's pools two trials of up to 72 weeks, one in adults without type 2 diabetes and one in adults with it. Zepbound's pools two trials of up to 72 weeks. The trials, doses and people differ, so compare each product with its own placebo group more than with the other columns.

Stopping because of side effects

The labels also report how many people left the trials because of side effects. In the Wegovy pill label's trial (204 adults treated for up to 64 weeks), 6.9% on the tablet stopped because of adverse reactions, against 5.9% on placebo. Foundayo's label reports 8% against 3% in its pooled trials. Zepbound's reports 4.8%, 6.3% and 6.7% across its three strengths against 3.4% on placebo.

In the published papers, 5.3% to 10.3% of people on Foundayo's three trial doses stopped for this reason against 2.7% on placebo (ATTAIN-1), and 4.3%, 7.1% and 6.2% on Zepbound's three doses against 2.6% (SURMOUNT-1). In SURMOUNT-1, most digestive effects came during dose increases. The week-by-week side effects page shows when they tend to appear.

What the labels say about taking each one

The biggest practical difference on paper is the pill rules. The Wegovy pill label asks for the tablet to be taken in the morning on an empty stomach with up to 4 ounces of plain water, with a wait of at least 30 minutes before food, other drinks or other oral medicines. Foundayo's label says with or without food and gives no time-of-day rule. The two injection labels say any time of day, with or without meals.

Both pill labels say the medicine slows stomach emptying and can change how other oral medicines are absorbed. Foundayo's label also has a line on oral hormonal contraceptives: it advises patients using them to switch to a non-oral method or add a barrier method for 30 days after starting and for 30 days after each dose increase. The birth control and pregnancy page covers what the other labels say. Both pill labels also list a warning about pulmonary aspiration during general anesthesia or deep sedation, which the surgery, anesthesia and colonoscopy page explains.

Heart and other label uses

The Wegovy label lists a cardiovascular use for both of its forms, for adults with established cardiovascular disease and obesity or overweight. SELECT, a trial of the injection, found major cardiovascular events in 6.5% of adults on semaglutide 2.4 mg and 8.0% on placebo. The Atlas did not read the part of the label that explains what supports the tablets' cardiovascular use. Foundayo's label lists no cardiovascular use. A placebo-controlled cardiovascular outcomes trial of orforglipron is registered and recruiting (NCT07241390, 7,140 planned participants).

Zepbound's label adds obstructive sleep apnea, and the Wegovy injection label adds MASH and use from age 12. These differences come from the labels and say nothing about weight-loss averages.

Moving from a shot to a pill, or back

The Wegovy label includes a section on moving between its own injection and its tablets, and the switching page summarizes what current labels say. The Atlas does not give steps. Controlled evidence is thin: ATTAIN-MAINTAIN is the one published randomized trial of a pill after weight loss on injections, it lasted a year, and Eli Lilly sponsored it.

Which one is right for me?

A table of trial averages cannot answer that. A prescriber weighs your diagnoses, your other medicines, how you handle side effects and food rules, what your plan covers, what is in stock and what you can afford. The first visit page and the questions to ask your prescriber help you prepare, and the paying for GLP-1 medicines page covers the main ways people pay.

What about compounded versions?

Compounded versions are made by pharmacies, are not FDA-approved and are not reviewed by the FDA for safety, effectiveness or quality before they are sold. The numbers on this page describe the approved products. See compounded versus brand-name medicines and the weight-loss pills guide for how the two approved pills compare with each other and with older pills.

Quick answers

Is the Wegovy pill as effective as the Wegovy injection?

The pill and the injection have not been tested against each other. In separate trials, average weight change was -13.6% on the pill at 64 weeks (OASIS 4, 307 adults) and -14.9% on the injection at 68 weeks (STEP 1, 1,961 adults), against -2.2% and -2.4% on placebo. The trials differ in size, length and, in the case of OASIS 4, an analysis the abstract does not name, so the Atlas does not call one stronger.

Is Foundayo as effective as Zepbound?

No trial has compared them. Both main trials ran 72 weeks and report effects regardless of whether people stayed on treatment. Foundayo's highest trial dose averaged -11.2% (ATTAIN-1) and Zepbound's highest dose averaged -20.9% (SURMOUNT-1), against -2.1% and -3.1% on placebo. The two trials had different people and different makers, and nothing compares the products directly.

Do the pills need an empty stomach?

The Wegovy pill label says to take the tablet in the morning on an empty stomach with water and to wait at least 30 minutes before eating, drinking or taking other oral medicines. Foundayo's label says to take it with or without food.

Do the pills cause fewer side effects than the injections?

The labels list the same kinds of digestive effects for all four products. The percentages come from different trials, doses and people, so the Atlas does not rank them. In OASIS 4, any digestive event was reported by 74.0% on the Wegovy pill and 42.2% on placebo.

Do the pills carry the same boxed warning as the injections?

All four labels carry a boxed warning about thyroid C-cell tumors. Foundayo's says orforglipron did not produce tumors in rodents, unlike other GLP-1 medicines, and that the human relevance has not been determined.

Has anyone compared a weight-loss pill with a weight-loss injection?

The Atlas found no such trial in adults with obesity. The nearest are SURMOUNT-5, which compared two injections, and ATTAIN-MAINTAIN, which tested a pill after injections but had no group that stayed on the shot.

Can a pill keep weight off after injections?

ATTAIN-MAINTAIN tested orforglipron, the medicine in Foundayo, against placebo in adults who had lost weight on weekly tirzepatide or semaglutide. The pill group kept more of the weight reduction over 52 weeks. The trial had no group that stayed on the injection, and Eli Lilly sponsored it.

Which is cheaper, the pill or the shot?

Prices, coverage rules and offers change often, and they differ by plan. The paying for GLP-1 medicines page covers how people pay, and the cost tool adds up listed prices over a year.

Are other weight-loss pills in trials?

Yes. One example is LY4086940, an oral medicine from Eli Lilly. Its phase 1 trial has finished and a phase 2 trial is registered, but no dose or results are public and it is not approved. The pipeline page lists the medicines in trials, and the weight-loss pills guide covers the pills available now.

Questions to ask

• Which of these products match the use on my diagnosis, and how does my plan cover each one?
• Can I follow the food and timing rules on the pill's label in my daily routine?
• Which of my other medicines are taken by mouth, and could slower stomach emptying matter for them?
• What is the plan if the first product does not suit me?
• What would each product cost me with my coverage, including after the first month?

What is still unknown

• The Atlas found no head-to-head trial of a weight-loss pill against a weight-loss injection in adults with obesity.
• The OASIS 4 abstract does not name its analysis, and the Atlas could not read the efficacy section of the Wegovy label for the pill, so the 13.6% figure is the abstract's estimated mean change.
• The Wegovy pill's main weight trial was smaller and shorter than the injection program. OASIS 4 followed 307 adults for 64 weeks, while STEP 1 had 1,961 adults and SELECT, a trial of the injection, followed 17,604 adults for an average of 39.8 months. Foundayo's ATTAIN-1 was large (3,127 adults) but ran 72 weeks.
• How closely people follow the Wegovy pill's timing rules outside a trial, and what that does to results, has not been measured in the sources the Atlas read.
• Eli Lilly has registered a head-to-head of orforglipron against oral semaglutide in adults with type 2 diabetes (ACHIEVE-3, NCT06045221). The Atlas has not read its results, and it is a diabetes trial, not a weight-loss trial.
• The Atlas read the published abstracts of the trials and the FDA-hosted labels, not the full papers, so it does not list every side-effect rate. Labels change, so check the current ones.