Orforglipron vs semaglutide
Orforglipron (Foundayo) is a daily GLP-1 pill that isn’t a peptide. Semaglutide comes as a weekly injection and as daily tablets with strict fasting rules. In type 2 diabetes, orforglipron lowered HbA1c more than semaglutide tablets.
- Orforglipron
- Approved drugOnce daily
- Semaglutide
- Approved drugOnce weekly
- Head-to-head trials
- 1
The short answer
Both act on the GLP-1 receptor. Semaglutide is a peptide, injected once a week (Wegovy, Ozempic) or taken as a daily tablet (Rybelsus and Ozempic tablets for type 2 diabetes, and a Wegovy tablet for weight). Orforglipron is a small molecule, approved on April 1, 2026 as Foundayo, a daily tablet for weight management.
Semaglutide’s diabetes tablets must be taken on an empty stomach with no more than 4 ounces of water, then nothing else for 30 minutes. Foundayo can be taken at any time of day, with or without food. In ACHIEVE-3, orforglipron lowered HbA1c 1.91 points vs 1.47 on semaglutide tablets 14 mg over 52 weeks, though more people stopped it for side effects. For weight, injected semaglutide’s trials show larger losses than orforglipron’s, but no trial has compared those two directly.
At a glance
| Field | OrforglipronFoundayo, LY3502970 | SemaglutideActive ingredient in Ozempic and Wegovy |
|---|---|---|
| Evidence | Approved drug | Approved drug |
| Class | Oral small-molecule GLP-1 receptor agonist | GLP-1 receptor agonist |
| Approval | Approved in the US on April 1, 2026 as Foundayo tablets for weight management in adults with obesity, or overweight with a weight-related condition; it was the first new drug approved through FDA’s national priority voucher program. The UK’s MHRA authorized it in August 2026. Not approved for type 2 diabetes as of early October 2026. | Approved in the US as Wegovy (weight management, heart risk, MASH) and as Ozempic and Rybelsus (type 2 diabetes), as weekly injections and daily tablets. |
| Sport (WADA 2026) | Not banned in sport | Not banned in sport |
| Common dose | 0.8 → 17.2 mg daily | 0.25 → 2.4 mg weekly |
| Frequency | Once daily | Once weekly |
| Cycle | Continuous | Continuous |
| Route | By mouth (tablet) | Subcutaneous injection |
| Half-life | about 29 to 49 hours Label | about 1 week Label |
| Typical draw | – | 5 units10 mg with 2 mL, 0.25 mg |
| Vial sizes or form | 0.8–17.2 mg tablets | 10, 20 mg |
| Human studies | 5 listedLargest: 3,127 people (2025) | 5 listedLargest: 17,604 people (2023) |
| Main cautions |
|
|
| Open Orforglipron | Open Semaglutide |
Doses shown are what labels, trials or community reports reference, not recommendations. Each compound’s page has the full detail and sources.
Key differences
What they are
Semaglutide is a 31-amino-acid peptide with a fatty-acid chain. Orforglipron is a non-peptide small molecule.
How they’re taken
LabelSemaglutide: a weekly injection, or a daily tablet on an empty stomach with up to 4 ounces of water and a 30-minute wait before food, drink or other pills (Rybelsus and Ozempic tablets label). Orforglipron: one tablet a day, any time, with or without food (Foundayo label).
Approved uses
LabelSemaglutide: type 2 diabetes with heart and kidney protection, weight management, heart risk and MASH. Orforglipron: weight management in adults; not approved for type 2 diabetes as of early October 2026.
Results
TrialType 2 diabetes, head to head: HbA1c fell 1.71 and 1.91 points on orforglipron 12 and 36 mg capsules vs 1.23 and 1.47 on semaglutide tablets 7 and 14 mg (ACHIEVE-3, 52 weeks). Weight, separate trials: orforglipron 17.2 mg, 11.1% at 72 weeks (ATTAIN-1); injected semaglutide 2.4 mg, 14.9% at 68 weeks (STEP 1).
Half-life
LabelSemaglutide: about 1 week. Orforglipron: about 29 to 49 hours, reaching steady state after about a week of daily doses.
Interactions
LabelFoundayo’s label caps the dose at 9 mg with strong CYP3A4 inhibitors, keeps simvastatin at 20 mg or less, and warns that birth-control pills may work less well for 30 days after starting and after each step up.
Head-to-head studies
The published trial that compared them directly.
-
HbA1c fell 1.71 and 1.91 points vs 1.23 and 1.47 on semaglutide in type 2 diabetes on metformin; 9–10% stopped for side effects vs 4–5%.
- Design
- Randomized open-label trial vs oral semaglutide (phase 3)
- Dose
- 12 or 36 mg capsules daily vs oral semaglutide 7 or 14 mg
- Length
- 52 weeks
Rosenstock et al., Lancet 2026 (ACHIEVE-3), PMID 41765029
Taking them together
Orforglipron and semaglutide both act on the GLP-1 receptor. The Wegovy and Zepbound labels say not to combine them with any other GLP-1 receptor agonist.
Source: Wegovy and Zepbound prescribing information, section 1
Open them in the stack check for sport status and one combined tracking checklist.
Questions
What is the difference between orforglipron and semaglutide?
Both act on the GLP-1 receptor. Semaglutide is a peptide, injected once a week (Wegovy, Ozempic) or taken as a daily tablet (Rybelsus and Ozempic tablets for type 2 diabetes, and a Wegovy tablet for weight). Orforglipron is a small molecule, approved on April 1, 2026 as Foundayo, a daily tablet for weight management.
Is orforglipron better than semaglutide?
It depends on which semaglutide. Against semaglutide tablets in type 2 diabetes, orforglipron lowered HbA1c more (ACHIEVE-3), with more people stopping for side effects (9–10% vs 4–5%). Against injected semaglutide there is no head-to-head trial; semaglutide’s weight-loss trials report larger losses, but in different people over different lengths of time.
Do you have to fast to take orforglipron?
No. Foundayo’s label says to take it once a day with or without food. Semaglutide’s diabetes tablets are different: they need an empty stomach, no more than 4 ounces of water and a 30-minute wait before eating.
Can orforglipron and semaglutide be taken together?
The stack check flags two GLP-1 drugs. Orforglipron and semaglutide both act on the GLP-1 receptor. The Wegovy and Zepbound labels say not to combine them with any other GLP-1 receptor agonist. No published study has tested them together.
Which has more evidence in people, orforglipron or semaglutide?
Orforglipron is approved in the US; its page lists 5 key human studies. Semaglutide is approved in the US; its page lists 5 key human studies. They have been compared directly in one trial, described on this page.
Are orforglipron and semaglutide banned in sport?
Orforglipron and semaglutide aren’t banned. This follows the WADA 2026 Prohibited List; athletes should confirm with their anti-doping organization.
Sources
- Foundayo prescribing information, rev. 07/2026 (Eli Lilly)
- Rybelsus and Ozempic tablets prescribing information (Novo Nordisk, DailyMed, August 2026)
- Rosenstock et al., orforglipron vs oral semaglutide, ACHIEVE-3 (Lancet 2026) PMID 41765029
- Wharton et al., orforglipron for obesity, ATTAIN-1 (NEJM 2025) PMID 40960239
- Wilding et al., semaglutide for obesity, STEP 1 (NEJM 2021) PMID 33567185
Each compound’s page lists its full sources: Orforglipron, Semaglutide.