# Orforglipron vs Semaglutide: How They Differ | PepVault

Source: https://pepvault.app/peptides/compare/orforglipron-vs-semaglutide

Last updated: 2026-10-06

[Library](https://pepvault.app/peptides) [Comparisons](https://pepvault.app/peptides/compare) Orforglipron vs Semaglutide

Compared side by side

# Orforglipron vs semaglutide: how they differ

Reviewed October 2026 [How we check the library](https://pepvault.app/about#library)

## The short answer

Both act on the GLP-1 receptor, but orforglipron is a small molecule (not a peptide) taken as a daily tablet, with or without food, while semaglutide is given as a weekly shot. Both are FDA-approved for weight management, orforglipron as Foundayo since April 2026. In their main trials, orforglipron’s top dose averaged about 11% weight loss at 72 weeks, and semaglutide about 15% at 68 weeks.

## Side by side

| Compared | [Orforglipron](https://pepvault.app/peptides/orforglipron) | [Semaglutide](https://pepvault.app/peptides/semaglutide) |
| --- | --- | --- |
| Category | Metabolic & GLP-1 | Metabolic & GLP-1 |
| Also known as | Foundayo, LY3502970, Orfo | Ozempic, Wegovy |
| What it is | A GLP-1 drug in a once-daily tablet that is not a peptide, so it comes with no fasting or water rules: Lilly's Foundayo, FDA-approved in April 2026 for weight management. | A GLP-1 receptor agonist that mimics a gut hormone your body releases after eating: it reduces appetite and slows stomach emptying. |
| How it works | Small-molecule (non-peptide) GLP-1 receptor agonist taken as a daily tablet. Because it is a small molecule it is absorbed without the fasting and water rules of oral semaglutide: the label puts its absolute bioavailability at 77% and lets it be taken with or without food. It reduces food intake, likely by lowering appetite, and delays stomach emptying, most after the first dose; in animal studies it reached and activated brain regions that regulate appetite. FDA-approved on April 1, 2026, as Foundayo for chronic weight management, at 0.8 to 17.2 mg once daily. | GLP-1 receptor agonist that reduces appetite, slows gastric emptying, and improves glucose metabolism. FDA-approved for T2DM and obesity. Titrate dose slowly to minimize GI side effects. |
| Commonly reported | The easy routine is the main draw, with nausea, constipation or burping mostly in the weeks after each step-up. Its top dose averaged about 11% weight loss at 72 weeks in its main trial. | The constant background thoughts about food ("food noise") go quiet and portions shrink without effort, with nausea worst in the first days after each dose step. FDA-approved for type 2 diabetes, weight management, heart-risk reduction and MASH, with about 15% average weight loss at 68 weeks in its main trial. |
| Studied range | FDA label: 0.8–17.2 mg, starting dose 0.8 mg. | FDA label: 0.25–2.4 mg, starting dose 0.25 mg. |
| How often | Daily | Weekly SubQ |
| Half-life | ~29–49 hours (FDA label; steady levels after about a week of daily tablets) | ~1 week (FDA label) |
| Route | Oral tablet | SubQ injection |
| Typical run | FDA-approved for long-term use alongside diet and activity. ATTAIN-MAINTAIN tested it as the follow-on to weekly injections for keeping weight off. | FDA-approved for ongoing use. Community uses indefinitely or until goal weight reached, then tapers. |
| Evidence | Established: clinical trials or FDA-approved use exists | Established: clinical trials or FDA-approved use exists |
| Common side effects | Nausea, constipation, diarrhea, vomiting, indigestion, abdominal pain, headache, burping | Nausea, vomiting, diarrhea, constipation, decreased appetite, fatigue, pancreatitis risk |

Typical run: Community practice — opinions vary. Not a clinical recommendation.

## Week by week

Each entry’s cards by day window, as the compound pages show them. Day 1 is the day you start it.

### Orforglipron

- Day 1–30 · 0.8 mg The 0.8 mg start
- Day 31–60 · 2.5 mg 2.5 mg, the second step
- Day 61+ · 5.5 mg 5.5 mg, the first maintenance dose
- Day 91+ · 9 mg 9 mg, an optional step
- Day 121+ · 14.5 mg 14.5 mg, the step before the top
- Day 151+ · 17.2 mg 17.2 mg, the top dose

[Every card for orforglipron, with its sources](https://pepvault.app/peptides/orforglipron#weeks)

### Semaglutide

- Day 1–28 · 0.25 mg Gut is adapting
- Day 29–56 · 0.5 mg Appetite shifts are real now
- Day 57–112 · 1 mg Clinically useful weight loss kicks in
- Day 113–140 · 1.7 mg Max submaximal step
- Day 141–364 · 2.4 mg Full dose — the working dose
- Day 365+ Plateau territory — new baseline

[Every card for semaglutide, with its sources](https://pepvault.app/peptides/semaglutide#weeks)

## Questions people ask

### How long do orforglipron and semaglutide last?

The half-life of orforglipron is ~29–49 hours (FDA label; steady levels after about a week of daily tablets). The half-life of semaglutide is ~1 week (FDA label).

### How often are orforglipron and semaglutide taken?

Orforglipron: daily. Route: Oral tablet. Semaglutide: weekly SubQ. Route: SubQ injection.

### How are orforglipron and semaglutide dosed in research?

The FDA label range for orforglipron is 0.8–17.2 mg, with a 0.8 mg starting dose. The FDA label range for semaglutide is 0.25–2.4 mg, with a 0.25 mg starting dose.

### What are the common side effects of orforglipron and semaglutide?

For orforglipron, the library lists: nausea, constipation, diarrhea, vomiting, indigestion, abdominal pain, headache, burping. For semaglutide: nausea, vomiting, diarrhea, constipation, decreased appetite, fatigue, pancreatitis risk.

## Each one in full

- [Orforglipron: dosage, half-life & reference guide](https://pepvault.app/peptides/orforglipron)
- [Semaglutide: dosage, half-life & reference guide](https://pepvault.app/peptides/semaglutide)
- [Orforglipron dose guide](https://pepvault.app/lab/dosage/orforglipron)
- [Semaglutide dose guide](https://pepvault.app/lab/dosage/semaglutide)

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## Track either one in PepVault

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## The library

- [The peptide reference library](https://pepvault.app/peptides)
- [Metabolic & GLP-1 peptides](https://pepvault.app/peptides#metabolic)

## Free tools

- [The Dose Guide](https://pepvault.app/lab/dosage)
- [Half-life & active level](https://pepvault.app/tools/peptide-half-life-calculator)
- [Reconstitution calculator](https://pepvault.app/tools/reconstitution-calculator)
- [GLP-1 titration planner](https://pepvault.app/tools/glp1-titration-calculator)

PepVault is a research and tracking resource, not medical advice. Ranges are what studies used, never a dose for you. Brand names are trademarks of their owners; PepVault is independent of them.

PepVault is a private research and tracking tool, not medical advice. The information here is reference material from published literature and community use — always verify it and discuss any protocol with a qualified clinician before changing it. Ozempic, Wegovy, Rybelsus, Mounjaro, Zepbound, Saxenda, Victoza and Trulicity are trademarks of their respective owners; PepVault is independent and not affiliated with or endorsed by any manufacturer.

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