The short answer
Semaglutide activates one receptor, GLP-1; retatrutide activates three, GLP-1, GIP and glucagon, and its glucagon arm adds energy expenditure (shown so far in mice). Semaglutide is FDA-approved, as Ozempic and Wegovy, and retatrutide isn’t approved yet. In their own trials, semaglutide averaged about 15% weight loss at 68 weeks, and retatrutide’s top dose about 25–28% at 80 weeks in phase 3.
Side by side
| Compared | Retatrutide | Semaglutide |
|---|---|---|
| Category | Metabolic & GLP-1 | Metabolic & GLP-1 |
| Also known as | LY3437943 | Ozempic, Wegovy |
| What it is | The first triple agonist to reach phase 3: it activates GLP-1, GIP and glucagon receptors at once, and the glucagon arm adds extra calorie burn (shown in mice). | 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 | Triple GIP/GLP-1/glucagon receptor agonist. Produces large weight loss through appetite suppression and improved metabolic function; the glucagon arm adds energy expenditure, shown so far in mice. Its trials step the dose up every 4 weeks because GI side effects rise with the dose; in phase 2 they were milder with a 2 mg start than a 4 mg one. | 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 | Appetite suppression even stronger than tirzepatide, GI side effects after each step-up, and a higher resting heart rate. Its top dose averaged about 25–28% weight loss at 80 weeks in phase 3; it isn't approved yet. | 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 | Research range: 1–12 mg, starting dose 2 mg. Studied in research — not a recommendation. | FDA label: 0.25–2.4 mg, starting dose 0.25 mg. |
| How often | Weekly | Weekly SubQ |
| Half-life | ~6 days (measured in early trials in people) | ~1 week (FDA label) |
| Route | SubQ injection | SubQ injection |
| Typical run | Phase 3 trials use continuous dosing. Community mirrors this — long-term with slow titration. | 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, vomiting, diarrhea, constipation, decreased appetite, fatigue, abdominal pain | Nausea, vomiting, diarrhea, constipation, decreased appetite, fatigue, pancreatitis risk |
- Category
- RetatrutideMetabolic & GLP-1
- SemaglutideMetabolic & GLP-1
- Also known as
- RetatrutideLY3437943
- SemaglutideOzempic, Wegovy
- What it is
- RetatrutideThe first triple agonist to reach phase 3: it activates GLP-1, GIP and glucagon receptors at once, and the glucagon arm adds extra calorie burn (shown in mice).
- 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
- RetatrutideTriple GIP/GLP-1/glucagon receptor agonist. Produces large weight loss through appetite suppression and improved metabolic function; the glucagon arm adds energy expenditure, shown so far in mice. Its trials step the dose up every 4 weeks because GI side effects rise with the dose; in phase 2 they were milder with a 2 mg start than a 4 mg one.
- 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
- RetatrutideAppetite suppression even stronger than tirzepatide, GI side effects after each step-up, and a higher resting heart rate. Its top dose averaged about 25–28% weight loss at 80 weeks in phase 3; it isn't approved yet.
- 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
- RetatrutideResearch range: 1–12 mg, starting dose 2 mg. Studied in research — not a recommendation.
- SemaglutideFDA label: 0.25–2.4 mg, starting dose 0.25 mg.
- How often
- RetatrutideWeekly
- SemaglutideWeekly SubQ
- Half-life
- Retatrutide~6 days (measured in early trials in people)
- Semaglutide~1 week (FDA label)
- Route
- RetatrutideSubQ injection
- SemaglutideSubQ injection
- Typical run
- RetatrutidePhase 3 trials use continuous dosing. Community mirrors this — long-term with slow titration.
- SemaglutideFDA-approved for ongoing use. Community uses indefinitely or until goal weight reached, then tapers.
- Evidence
- RetatrutideEstablished: clinical trials or FDA-approved use exists
- SemaglutideEstablished: clinical trials or FDA-approved use exists
- Common side effects
- RetatrutideNausea, vomiting, diarrhea, constipation, decreased appetite, fatigue, abdominal pain
- 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.
Retatrutide
- Day 1–28 · 2 mg Triple-agonist is kicking in
- Day 29–84 · 4 mg Dose-response steepens
- Day 60+ · 9 mg Watch for dysesthesia at higher doses
- Day 84+ This is a maintenance medication, not a course
- Day 85–168 · 8 mg Higher steps: strong satiety
- Day 169–336 No plateau yet at week 48
- Day 337–476 Phase 3 territory: the headline numbers
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 retatrutide and semaglutide last?
The half-life of retatrutide is ~6 days (measured in early trials in people). The half-life of semaglutide is ~1 week (FDA label).
How often are retatrutide and semaglutide taken?
Retatrutide: weekly. Route: SubQ injection. Semaglutide: weekly SubQ. Route: SubQ injection.
How are retatrutide and semaglutide dosed in research?
The research range for retatrutide is 1–12 mg, with a 2 mg starting dose. Studied in research — not a recommendation. 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 retatrutide and semaglutide?
For retatrutide, the library lists: nausea, vomiting, diarrhea, constipation, decreased appetite, fatigue, abdominal pain. 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 retatrutide or semaglutide, with reminders on your schedule. 7 days free on the yearly plan for new subscribers.
