# Retatrutide vs Semaglutide: How They Differ | PepVault

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

Last updated: 2026-10-12

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

Compared side by side

# Retatrutide vs semaglutide: how they differ

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

## 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](https://pepvault.app/peptides/retatrutide) | [Semaglutide](https://pepvault.app/peptides/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 |

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

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

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

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.

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## More comparisons

- [All peptide comparisons](https://pepvault.app/peptides/compare)
- [Retatrutide vs Tirzepatide](https://pepvault.app/peptides/compare/retatrutide-vs-tirzepatide)
- [Semaglutide vs Tirzepatide](https://pepvault.app/peptides/compare/semaglutide-vs-tirzepatide)
- [Survodutide vs Retatrutide](https://pepvault.app/peptides/compare/survodutide-vs-retatrutide)
- [Orforglipron vs Semaglutide](https://pepvault.app/peptides/compare/orforglipron-vs-semaglutide)
- [Cagrilintide vs Semaglutide](https://pepvault.app/peptides/compare/cagrilintide-vs-semaglutide)
- [Liraglutide vs Semaglutide](https://pepvault.app/peptides/compare/liraglutide-vs-semaglutide)

## 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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