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 | 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 |
- Category
- OrforglipronMetabolic & GLP-1
- SemaglutideMetabolic & GLP-1
- Also known as
- OrforglipronFoundayo, LY3502970, Orfo
- SemaglutideOzempic, Wegovy
- What it is
- OrforglipronA 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.
- SemaglutideA GLP-1 receptor agonist that mimics a gut hormone your body releases after eating: it reduces appetite and slows stomach emptying.
- How it works
- OrforglipronSmall-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.
- SemaglutideGLP-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
- OrforglipronThe 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.
- SemaglutideThe 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
- OrforglipronFDA label: 0.8–17.2 mg, starting dose 0.8 mg.
- SemaglutideFDA label: 0.25–2.4 mg, starting dose 0.25 mg.
- How often
- OrforglipronDaily
- SemaglutideWeekly SubQ
- Half-life
- Orforglipron~29–49 hours (FDA label; steady levels after about a week of daily tablets)
- Semaglutide~1 week (FDA label)
- Route
- OrforglipronOral tablet
- SemaglutideSubQ injection
- Typical run
- OrforglipronFDA-approved for long-term use alongside diet and activity. ATTAIN-MAINTAIN tested it as the follow-on to weekly injections for keeping weight off.
- SemaglutideFDA-approved for ongoing use. Community uses indefinitely or until goal weight reached, then tapers.
- Evidence
- OrforglipronEstablished: clinical trials or FDA-approved use exists
- SemaglutideEstablished: clinical trials or FDA-approved use exists
- Common side effects
- OrforglipronNausea, constipation, diarrhea, vomiting, indigestion, abdominal pain, headache, burping
- SemaglutideNausea, 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
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
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
PepVault for iPhone
Track either one in PepVault
Log every dose of orforglipron or semaglutide, with reminders on your schedule. 7 days free on the yearly plan for new subscribers.
