Orforglipron is a once-daily GLP-1 pill from Eli Lilly, sold in the US as Foundayo. In the main obesity trial, ATTAIN-1, people on the top dose lost 11.2% of their body weight over 72 weeks, compared with 2.1% on placebo. In a head-to-head diabetes trial it lowered A1C more than oral semaglutide (Rybelsus), but more people stopped it because of side effects. This article walks through what each published trial found, with the exact numbers, and how this pill differs from the semaglutide pills.
For the label dose steps and missed-dose rule, see our Foundayo dosing guide.
Semaglutide, tirzepatide and liraglutide are peptides, meaning small proteins. Peptides are hard to absorb by mouth: the semaglutide pills need an added absorption helper and Rybelsus still gets only 0.4% to 1% of the dose into the blood (Rybelsus label, 12.3). Orforglipron is a small molecule, not a peptide. The trial papers call it a "nonpeptide" GLP-1 receptor agonist: it switches on the same receptor, but it is built like an ordinary pill drug (Rosenstock 2025). Foundayo tablets contain no absorption helper (Foundayo label, 11).
The FDA approved Foundayo in 2026. Its label covers one use: lowering excess body weight and keeping it off long term, with diet and exercise, in adults with obesity, or with overweight plus at least one weight-related health problem (Foundayo label, 1). Several of the trials below were in type 2 diabetes, but the label we read does not list diabetes treatment as a use.
This trips people up. The trials used an investigational formulation dosed at 3, 6, 12 or 36 mg. The Foundayo label reports the same weight trials but shows the doses as the equivalent Foundayo tablets: 5.5, 9 and 17.2 mg (Foundayo label, 6.1 and 14). The ACHIEVE-4 paper states the link directly for the top dose: a 36 mg capsule is "equivalent to 17·2 mg tablet" (Klein 2026). The label's group sizes (329, 332 and 322 people) also match the 6, 12 and 36 mg arms of ATTAIN-2. So paper doses of 6, 12 and 36 mg appear on the label as 5.5, 9 and 17.2 mg. Below we use the dose each source used.
ATTAIN-1 enrolled 3,127 adults with obesity, or overweight plus a related condition, and no diabetes. They took 6, 12 or 36 mg once a day, or placebo, for 72 weeks, with diet and activity advice (Wharton 2025).
| ATTAIN-1, week 72 | Weight change | Stopped for side effects |
|---|---|---|
| Placebo | -2.1% | 2.7% |
| 6 mg | -7.5% | 5.3% to 10.3% across doses |
| 12 mg | -8.4% | |
| 36 mg | -11.2% |
On 36 mg, 54.6% of people lost at least 10% of their weight, 36.0% lost at least 15%, and 18.4% lost at least 20%. On placebo those shares were 12.9%, 5.9% and 2.8%. Waist size, blood pressure and blood fats also improved more than on placebo (Wharton 2025).
The label reports its own analysis of the same trial, so the numbers differ slightly: -7.4%, -8.3% and -11.1% on 5.5, 9 and 17.2 mg, against -2.1% on placebo. The label also reports that 22% to 24% of people on the drug stopped the trial drug early, compared with 30% on placebo (Foundayo label, 14, Table 6).
ATTAIN-2 tested the same doses for 72 weeks in 1,613 adults with a BMI of 27 or more and type 2 diabetes, with a starting A1C of 7% to 10%. Weight loss was smaller than in ATTAIN-1 (Horn 2025):
A1C also improved. Stopping because of side effects, mostly stomach-related, happened in 6.1% to 9.9% of people on orforglipron and 4.1% on placebo.
ACHIEVE-1 was the first phase 3 result. It enrolled 559 adults with type 2 diabetes managed with diet and exercise alone, with an A1C of 7.0% to 9.5%. They took 3, 12 or 36 mg, or placebo, for 40 weeks. A1C is a blood test that reflects average blood sugar over about three months (Rosenstock 2025).
| ACHIEVE-1, week 40 | A1C change (points) | Weight change |
|---|---|---|
| Placebo | -0.41 | -1.7% |
| 3 mg | -1.24 | -4.5% |
| 12 mg | -1.47 | -5.8% |
| 36 mg | -1.48 | -7.6% |
Starting A1C averaged 8.0%, and people on orforglipron ended at 6.5% to 6.7% on average. No one had severe low blood sugar. Stopping for side effects happened in 4.4% to 7.8% on orforglipron and 1.4% on placebo.
This is the trial most people ask about, because it compares two GLP-1 pills directly. ACHIEVE-3 enrolled 1,698 adults with type 2 diabetes not controlled on metformin and randomly assigned them to orforglipron 12 or 36 mg or oral semaglutide 7 or 14 mg for 52 weeks. People knew which drug they were taking (Rosenstock 2026).
| ACHIEVE-3, week 52 | A1C change | Stomach side effects | Stopped for side effects |
|---|---|---|---|
| Oral semaglutide 7 mg | -1.23% | 37% | 4% |
| Oral semaglutide 14 mg | -1.47% | 45% | 5% |
| Orforglipron 12 mg | -1.71% | 59% | 9% |
| Orforglipron 36 mg | -1.91% | 58% | 10% |
Both orforglipron doses beat both semaglutide doses on A1C, starting from an average of 8.3%. Orforglipron 36 mg beat semaglutide 14 mg by 0.44 points. The trade-off is in the other columns: more stomach side effects, about twice the rate of stopping, and a larger rise in resting pulse (3.7 to 4.7 beats per minute on orforglipron vs 1.0 to 1.5 on semaglutide).
The semaglutide doses here are the Rybelsus diabetes doses, not the 25 mg Wegovy pill used for weight loss, so this trial says nothing about that comparison.
The ACHIEVE-1, -2, -3 and -4 and ATTAIN-1 and -2 papers all list Eli Lilly, the maker of orforglipron, as the funder.
The Foundayo label pools the two weight trials, covering 3,155 people on the drug. Its main points (Foundayo label, 5 and 6.1):
See also GLP-1 side effects week by week. Dose Track lets you log each tablet and note side effects on the day they happen, so you can see whether they settle after a dose step and show your prescriber.
Semaglutide pills (Rybelsus, the Ozempic tablets and the Wegovy pill) carry an absorption helper called SNAC and are absorbed mainly in the stomach, and their labels set strict morning rules. Foundayo's label has none. What the labels say:
| Label says | Foundayo (orforglipron) | Rybelsus / Wegovy pill (semaglutide) |
|---|---|---|
| Food | With or without food | Empty stomach, in the morning |
| Water | No limit stated | Up to 4 oz of plain water only |
| Wait after dose | None stated | At least 30 min before food, drinks or other pills |
| Share absorbed | 77% (0.8 mg dose) | About 0.4% to 2% |
| Half-life | About 29 to 49 hours | About 1 week |
| Steady state | About 1 week | 4 to 5 weeks (Rybelsus) |
Sources: Foundayo label 2.1 and 12.3; Rybelsus label 2.1 and 12.3; Wegovy label 2.1 and 12.3. A few notes on that table:
The thyroid boxed warning also reads differently. Most GLP-1 labels say the drug caused thyroid C-cell tumors in rodents. Foundayo's says orforglipron does not act on the rat or mouse GLP-1 receptor and did not cause tumors in rodents. The label still carries the boxed warning. We cover what that warning means in the GLP-1 thyroid cancer warning, explained.
Choosing between a pill and a shot comes down to routine, side effects and cost, which is a talk to have with your prescriber. For the injectables, see semaglutide vs tirzepatide.
This article is general information, not medical advice. Talk to your prescriber before you start, change or stop any medicine.