The short answer
Tirzepatide is a dual GIP/GLP-1 receptor agonist; retatrutide adds a third target, the glucagon receptor, whose arm adds energy expenditure (shown so far in mice). Tirzepatide is FDA-approved, as Mounjaro and Zepbound, and retatrutide isn’t approved yet. In their own trials, retatrutide’s top dose averaged about 25–28% weight loss at 80 weeks in phase 3, and tirzepatide’s 15 mg up to 22.5% at 72 weeks (SURMOUNT-1).
Side by side
| Compared | Retatrutide | Tirzepatide |
|---|---|---|
| Category | Metabolic & GLP-1 | Metabolic & GLP-1 |
| Also known as | LY3437943 | Mounjaro, Zepbound, LY3298176 |
| 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). | The first dual GIP/GLP-1 receptor agonist: it activates two gut-hormone pathways at once, and in a head-to-head trial it produced more weight loss than semaglutide (20.2% vs 13.7% at 72 weeks). |
| 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. | Dual GIP/GLP-1 receptor agonist. Significantly reduces body weight through appetite suppression, slowed gastric emptying, and improved insulin sensitivity. Approved for T2DM and obesity management. |
| 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. | Very strong appetite suppression and meals ending early, with nausea or tiredness for a day or two after the injection, mostly after dose increases. FDA-approved for diabetes (Mounjaro) and for weight management and sleep apnea (Zepbound). |
| Studied range | Research range: 1–12 mg, starting dose 2 mg. Studied in research — not a recommendation. | FDA label: 2.5–15 mg, starting dose 2.5 mg. |
| How often | Weekly | Weekly |
| Half-life | ~6 days (measured in early trials in people) | ~5 days (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. Titrate slowly upward. Community maintains on minimum effective dose. |
| 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, diarrhea, vomiting, constipation, abdominal pain, decreased appetite, fatigue |
- Category
- RetatrutideMetabolic & GLP-1
- TirzepatideMetabolic & GLP-1
- Also known as
- RetatrutideLY3437943
- TirzepatideMounjaro, Zepbound, LY3298176
- 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).
- TirzepatideThe first dual GIP/GLP-1 receptor agonist: it activates two gut-hormone pathways at once, and in a head-to-head trial it produced more weight loss than semaglutide (20.2% vs 13.7% at 72 weeks).
- 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.
- TirzepatideDual GIP/GLP-1 receptor agonist. Significantly reduces body weight through appetite suppression, slowed gastric emptying, and improved insulin sensitivity. Approved for T2DM and obesity management.
- 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.
- TirzepatideVery strong appetite suppression and meals ending early, with nausea or tiredness for a day or two after the injection, mostly after dose increases. FDA-approved for diabetes (Mounjaro) and for weight management and sleep apnea (Zepbound).
- Studied range
- RetatrutideResearch range: 1–12 mg, starting dose 2 mg. Studied in research — not a recommendation.
- TirzepatideFDA label: 2.5–15 mg, starting dose 2.5 mg.
- How often
- RetatrutideWeekly
- TirzepatideWeekly
- Half-life
- Retatrutide~6 days (measured in early trials in people)
- Tirzepatide~5 days (FDA label)
- Route
- RetatrutideSubQ injection
- TirzepatideSubQ injection
- Typical run
- RetatrutidePhase 3 trials use continuous dosing. Community mirrors this — long-term with slow titration.
- TirzepatideFDA-approved for ongoing use. Titrate slowly upward. Community maintains on minimum effective dose.
- Evidence
- RetatrutideEstablished: clinical trials or FDA-approved use exists
- TirzepatideEstablished: clinical trials or FDA-approved use exists
- Common side effects
- RetatrutideNausea, vomiting, diarrhea, constipation, decreased appetite, fatigue, abdominal pain
- TirzepatideNausea, diarrhea, vomiting, constipation, abdominal pain, decreased appetite, fatigue
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
Tirzepatide
- Day 1–28 · 2.5 mg Getting your gut acclimated
- Day 29–56 · 5 mg First therapeutic dose — weight drops
- Day 57–112 · 7.5 mg Dual agonism in full effect
- Day 113–168 · 12.5 mg Max titration reached
- Day 169–504 Weeks 24 to 72: where most people plateau
- Day 365+ A maintenance medication, not a course
Questions people ask
How long do retatrutide and tirzepatide last?
The half-life of retatrutide is ~6 days (measured in early trials in people). The half-life of tirzepatide is ~5 days (FDA label).
How often are retatrutide and tirzepatide taken?
Retatrutide: weekly. Route: SubQ injection. Tirzepatide: weekly. Route: SubQ injection.
How are retatrutide and tirzepatide 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 tirzepatide is 2.5–15 mg, with a 2.5 mg starting dose.
What are the common side effects of retatrutide and tirzepatide?
For retatrutide, the library lists: nausea, vomiting, diarrhea, constipation, decreased appetite, fatigue, abdominal pain. For tirzepatide: nausea, diarrhea, vomiting, constipation, abdominal pain, decreased appetite, fatigue.
Each one in full
PepVault for iPhone
Track either one in PepVault
Log every dose of retatrutide or tirzepatide, with reminders on your schedule. 7 days free on the yearly plan for new subscribers.
