# Retatrutide — dosage, half-life & reference guide | PepVault

Source: https://pepvault.app/peptides/retatrutide

Last updated: 2026-10-12

[Library](https://pepvault.app/peptides) [Metabolic & GLP-1](https://pepvault.app/peptides#metabolic) reviewed October 2026

# Retatrutide Dosage, half-life & reference guide

Also known as LY3437943

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).

- **Studied range:** 1–12 mg starting dose 2 mg
- **How often:** Weekly
- **Half-life:** ~6 days
- **Evidence:** Established
- **Route:** SubQ injection

Studied in research — not a recommendation.

[Retatrutide dose guide](https://pepvault.app/lab/dosage/retatrutide)

## 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.

**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.

### Half-life & active level

The half-life of Retatrutide is ~6 days (measured in early trials in people).

Here's how a typical Retatrutide schedule accumulates over four weeks (one-compartment estimate).

An estimate from the half-life above, not a measurement. See your own curve build live in [the half-life calculator](https://pepvault.app/tools/peptide-half-life-calculator).

## Where Retatrutide works.

- ### Appetite & metabolism

  **In people.** Its top dose averaged about 25–28% weight loss at 80 weeks in phase 3.

An area lights for what a peptide is used for and what people report, with the evidence beside it. It isn’t a promise that it works there.

## Week by week.

What to expect in the first 8 weeks

- **Onset:** Days–2 weeks
- **Peak effect:** 48+ weeks
- **Duration:** Ongoing

1. Day 1–28 · 2 mg RCT

   ### Triple-agonist is kicking in

   You're on the 2mg run-in. Commonly reported: appetite visibly dropping this week and some mild nausea. The glucagon arm adds energy expenditure too, though that has only been measured in mice.

   The science

   In the phase 2 obesity trial (Jastreboff 2023 NEJM), GI side effects were dose-related and milder when dosing started at 2mg rather than 4mg; the trial had no semaglutide arm. Early heart rate can bump up modestly from glucagon — monitor if you've got baseline tachyarrhythmia.

   Sources

   - Jastreboff et al. (2023)

   Updated Sep 2026
2. Day 29–84 · 4 mg RCT

   ### Dose-response steepens

   You're at 4mg. Commonly reported: visible scale movement and durable appetite suppression. In phase 2 the 4mg arm averaged about 13% loss by week 24.

   The science

   In the Jastreboff 2023 phase 2 obesity trial, the 4mg arm reached −12.9% at 24 weeks and −17.1% at 48 weeks. The 2024 Sanyal paper in Nature Medicine documented an 82.4% relative reduction in liver fat at 12mg/24wk. Users commonly report GI tolerance settling within 1–2 weeks of a step-up.

   Sources

   - Jastreboff et al. (2023)
   - Sanyal et al. (2024)

   Updated Sep 2026
3. Any day RCT

   ### What Retatrutide is built on

   Reta is one of the most-studied compounds in this library that is not yet approved, with the largest phase 3 obesity result reported so far: multiple phase 2 trials plus a phase 3 program of over 5,800 people. It is not FDA-approved yet.

   The science

   Eli Lilly is the developer — same company behind Tirzepatide. Phase 2 peaked at −24.2% (Jastreboff 2023 NEJM). Three phase 3 trials are now peer-reviewed (2026): TRIUMPH-1 in NEJM (Jastreboff; 2,339 adults with obesity, 80wk: −25.0% at 12mg on the treatment-regimen estimand, plus less knee osteoarthritis pain and fewer sleep apnea events), and in The Lancet TRIUMPH-2 (1,152 adults with obesity and type 2 diabetes: −18.8% at 12mg vs −5.1% placebo) and TRANSCEND-T2D-1 (537 adults with type 2 diabetes). Lilly's TRIUMPH-1 topline adds −28.3% at 12mg had everyone stayed on treatment, 45.3% reaching ≥30% loss, and −30.3% by 104 weeks in the BMI ≥35 extension. Retatrutide is NOT FDA-approved; Lilly plans to file with the FDA in Q1 2027. Additional phase 3 readouts will characterize CV outcomes, CKD, MASH, and low back pain.

   Sources

   - Jastreboff et al. (2023)
   - Jastreboff et al. (TRIUMPH-1) (2026)
   - Lilly TRIUMPH-1 (2026)
   - Bellido et al. (TRIUMPH-2) (2026)
   - Bajaj et al. (TRANSCEND-T2D-1) (2026)

   Updated Oct 2026
4. Any day Clinical

   ### Protein + lifting protect lean mass

   Rapid loss on a triple-agonist isn't all fat — across the GLP-1 class, roughly a quarter to 40% of the weight lost is lean mass. The lever you control: keep protein high (about 1.6–2.2g/kg) and keep training resistance through the cut. The peptide handles appetite; protein and lifting decide what the loss is made of.

   The science

   SURMOUNT-class body-composition data put lean mass at ~25–40% of total weight lost on incretin therapy. Trials pairing muscle-sparing agents with GLP-1s are moving the field: bimagrumab + semaglutide produced ~22% total loss with ~92% from fat, and apitegromab + tirzepatide (EMBRAZE) spared roughly 1.9kg of lean mass vs tirzepatide alone. None of those add-ons is standard care; protein intake and resistance training are the evidence-backed levers available now.

   Sources

   - EMBRAZE (2025)

   Updated Jun 2026
5. With BPC-157 Community

   ### Why people add BPC-157 to Reta

   Titrating up on Reta can be rough on the gut — especially the later transitions — and BPC-157 is added to ease it. Commonly reported: smoother step-ups with fewer GI side effects. One of the most common Reta pairings.

   The science

   BPC-157 comes from a "body protection compound" first isolated from human gastric juice, and its early animal research was on gastric protection: mucosal integrity, gut-brain axis modulation, reduced NSAID damage. That fit with the GLP-1 side-effect profile is why the community stack emerged. No controlled trial of the combo exists.

   Sources

   - Sikiric et al. (2018)

   Updated Sep 2026

### After week 8

1. Day 60+ · 9 mg RCT

   ### Watch for dysesthesia at higher doses

   Heads up: at the higher steps, some phase 3 participants reported dysesthesia, an abnormal skin sensation such as tingling, burning or extra sensitivity, usually mild to moderate and mostly resolving on treatment. It's more common at higher doses. If you notice it, your clinician may want to hold the next step-up.

   The science

   TRIUMPH-1 (May 2026) reported dysesthesia in 5.1% at 4mg, 12.3% at 9mg and 12.5% at 12mg; TRIUMPH-4 reported 8.8% at 9mg and 20.9% at 12mg. Both trials used the same escalation (start at 2mg, step up every 4 weeks), so the gap between them isn't explained by titration speed. AE-driven discontinuation ran ~11.3% at 12mg. The mechanism isn't known; similar skin-sensation effects are listed for high-dose semaglutide (22% at 7.2mg vs 6% at 2.4mg in the Wegovy label). These are trial findings — discuss dose steps with your clinician.

   Sources

   - Lilly TRIUMPH-1 (2026)
   - Lilly TRIUMPH-4 (2025)
   - FDA Wegovy label (2026)

   Updated Sep 2026
2. Day 84+ Clinical

   ### This is a maintenance medication, not a course

   Worth knowing before you stop: across this class, coming off usually means regaining most of the loss — meta-analysis data show around 10kg back in the first year, trending toward baseline by roughly 18 months. Whether to continue, slow-taper, or stop is a decision for you and your clinician — just go in expecting a long-term relationship, not a fixed course.

   The science

   A BMJ meta-analysis (West 2026) and SURMOUNT-4 document substantial regain after stopping sema/tirz (~9.9kg in year 1, back to baseline by ~1.5 years), reflecting that incretin therapy treats an ongoing metabolic set point rather than curing it. Retatrutide has not been studied for discontinuation specifically, so this is class-level framing. The hold/taper/stop call is yours, made with your clinician.

   Sources

   - SURMOUNT-4 (2024)
   - West et al. (2026)

   Updated Sep 2026
3. Day 85–168 · 8 mg RCT

   ### Higher steps: strong satiety

   You're at 8mg, phase 2's middle dose (phase 3 steps through 6 and 9mg instead). Commonly reported: strong satiety and a clearly smaller waist. In phase 2, the 8 and 12mg arms averaged about 17% weight loss by week 24.

   The science

   Phase 2 (Jastreboff 2023 NEJM) used 8mg as a dose of its own, reached from a 2 or 4mg start with steps every 4 weeks: −17.3% at 24 weeks and −22.8% at 48 weeks. Phase 3 has no 8mg step; it goes 2 → 4 → 6 → 9 → 12mg, a step every 4 weeks. Sanyal et al. 2024 (Nature Medicine, MASLD) showed 82.4% relative liver fat reduction at 24wk in the 12mg arm, with 86% of patients reaching normal liver fat (<5%). The higher steps are also where dysesthesia (an abnormal skin sensation) becomes more common in phase 3: 12.3% at 9mg and 12.5% at 12mg in TRIUMPH-1. It is also listed for high-dose semaglutide.

   Sources

   - Jastreboff et al. (2023)
   - Sanyal et al. (2024)
   - Lilly TRIUMPH-1 (2026)

   Updated Oct 2026
4. Day 169–336 RCT

   ### No plateau yet at week 48

   In phase 2, weight hadn't plateaued by week 48: the 12mg arm reached −24.2% and the curve was still moving.

   The science

   Jastreboff 2023 phase 2: the 12mg arm hit −24.2% at 48wk vs −2.1% placebo, and 83% of that arm achieved ≥15% weight loss. In T2D patients (Rosenstock 2023 Lancet), HbA1c fell 2.02 points at 12mg vs 1.41 with dulaglutide at 24 weeks, and roughly 80% of 12mg patients reached HbA1c ≤6.5%.

   Sources

   - Jastreboff et al. (2023)
   - Rosenstock et al. (2023)

   Updated Sep 2026
5. Day 337–476 RCT

   ### Phase 3 territory: the headline numbers

   TRIUMPH-1 territory, the largest phase 3 obesity result reported so far and now published in NEJM. At 12mg, weight fell 25% on average by week 80, about 28% for people who stayed on treatment, and about 45% of them lost at least 30%. In people with a BMI of 35+ who kept going, the two-year mark reached about −30%.

   The science

   TRIUMPH-1 (Jastreboff 2026, NEJM; 2,339 adults with obesity and no diabetes, 80 weeks): −17.6% at 4mg, −23.7% at 9mg and −25.0% at 12mg vs −3.9% on placebo (treatment-regimen estimand, everyone randomized). It also cut knee osteoarthritis pain and sleep apnea events. Lilly's topline adds the efficacy estimand, had everyone stayed on treatment: −28.3% at 12mg, with 45.3% reaching ≥30% loss, and −30.3% at 104 weeks in an extension of people with a BMI of 35+ who had finished 80 weeks on treatment. With type 2 diabetes, TRIUMPH-2 (Bellido 2026, The Lancet; 1,152 adults) reached −18.8% at 12mg vs −5.1% on placebo at 80 weeks. The earlier TRIUMPH-4 topline (knee osteoarthritis) had shown −28.7% at 68wk. Retatrutide is not FDA-approved; Lilly plans to file with the FDA in Q1 2027, and approval timing isn't known.

   Sources

   - Jastreboff et al. (TRIUMPH-1) (2026)
   - Lilly TRIUMPH-1 (2026)
   - Bellido et al. (TRIUMPH-2) (2026)
   - Lilly TRIUMPH-4 (2025)

   Updated Oct 2026

Day 1 is the day you start it.

Phase 2 trial data (NEJM 2023), phase 3 trials (TRIUMPH-1, NEJM 2026; TRIUMPH-2, The Lancet 2026) and Lilly's phase 3 toplines. Not yet FDA-approved.

Moderate evidence

## Mixing and a typical run.

Example numbers

### Reconstitution example

Reconstitute a 10 mg vial of Retatrutide with 2 mL of bacteriostatic water and a 2 mg dose is 40 units on a U-100 syringe, about 5 doses per vial.

- **Vial:** 10 mg
- **Water:** 2 mL
- **Amount:** 2 mg

Draw to **40 units**

0.5 mL insulin syringe · 50 units

[Mix it in the Reconstitution Lab](https://pepvault.app/lab) [Open the calculator](https://pepvault.app/tools/reconstitution-calculator)

### Run notes

- **Cycle:** Phase 3 trials use continuous dosing. Community mirrors this — long-term with slow titration. Community practice — opinions vary. Not a clinical recommendation.
- **Timing:** Once weekly SubQ. In the phase 2 trial, doses stepped up every 4 weeks from a 2 or 4 mg start to 4, 8 or 12 mg, depending on the arm — trial escalations, not an approved regimen.
- **Route:** SubQ injection
- **Stacks:** BPC-157 (GI support)

## Safety.

### Common side effects

- Nausea
- Vomiting
- Diarrhea
- Constipation
- Decreased appetite
- Fatigue
- Abdominal pain

#### Interactions

As a GLP-1-class agent retatrutide slows gastric emptying, which can alter absorption of oral medications — a published, label-level consideration for the class; discuss timing of oral drugs with your clinician. Combined with insulin or sulfonylureas the additive glucose-lowering effect raises hypoglycemia risk in the class, warranting clinician-guided monitoring. Its glucagon-driven heart-rate effect is a noted consideration alongside sympathomimetics or in pre-existing tachyarrhythmia. No specific interaction data with SSRIs or anticoagulants beyond general clinical caution.

### Safety notes

In the Phase 2 obesity trial (Jastreboff et al., NEJM 2023), the most common adverse events were gastrointestinal: dose-related, mostly mild to moderate, concentrated during dose escalation and partly eased by a 2 mg rather than a 4 mg start (nausea in up to 60% of people in the 8 mg arm that started at 4 mg and 45% at 12 mg, plus vomiting, diarrhea and constipation). Serious adverse events were about as common as on placebo (10 of 267 on retatrutide vs 3 of 70, the trial's ClinicalTrials.gov results). In phase 3 (TRIUMPH-1, Lilly's topline), stopping for adverse events ran 4.1%, 6.9% and 11.3% at 4, 9 and 12 mg vs 4.9% on placebo. As a triple GIP/GLP-1/glucagon agonist it raised resting heart rate in a dose-dependent way; the rise peaked at week 24 and eased after. As a GLP-1-class agent it carries the class rodent thyroid C-cell signal and trial-monitored gallbladder/pancreatitis considerations. These are trial findings, not personal predictions — discuss with your clinician.

## Goes with.

- [BPC-157 GI support](https://pepvault.app/peptides/bpc-157)

- ### In the Metabolic Reset stack

  Triple-agonist appetite control + mitochondrial metabolic optimization

  With [MOTS-c](https://pepvault.app/peptides/mots-c)

## Compared with.

- [Retatrutide vs Tirzepatide](https://pepvault.app/peptides/compare/retatrutide-vs-tirzepatide)
- [Retatrutide vs Semaglutide](https://pepvault.app/peptides/compare/retatrutide-vs-semaglutide)
- [Survodutide vs Retatrutide](https://pepvault.app/peptides/compare/survodutide-vs-retatrutide)

## Questions people ask.

### What is Retatrutide?

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).

### How is Retatrutide dosed in research?

The research range for Retatrutide is 1–12 mg, weekly, with a 2 mg starting dose. Studied in research — not a recommendation.

### How long does Retatrutide last?

The half-life of Retatrutide is ~6 days (measured in early trials in people).

### What do people report on Retatrutide?

Commonly reported on Retatrutide: 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.

### Is Retatrutide safe?

The research basis for Retatrutide is established: clinical trials or FDA-approved use exists. Common side effects in the library: nausea, vomiting, diarrhea, constipation, decreased appetite, fatigue and abdominal pain.

### What does Retatrutide stack with?

Common stacks for Retatrutide: BPC-157 (GI support). Curated stacks with Retatrutide: Metabolic Reset.

## Research.

The literature

### Search the latest research

[PubMed](https://pubmed.ncbi.nlm.nih.gov/?term=Retatrutide) [Google Scholar](https://scholar.google.com/scholar?q=Retatrutide)

Guide

### [Retatrutide week by week](https://pepvault.app/guides/retatrutide-week-by-week)

Read the guide

Guide

### [What to take alongside each peptide](https://pepvault.app/guides/what-to-take-with-peptides)

Read the guide

## Reference.

- **Cadence:** Weekly
- **Half-life:** ~6 days ~6 days (measured in early trials in people)
- **Research basis:** Established Clinical trials or FDA-approved use exists

## More metabolic & glp-1 peptides

- [Liraglutide 0.6–3 mg](https://pepvault.app/peptides/liraglutide)
- [Dulaglutide 0.75–4.5 mg](https://pepvault.app/peptides/dulaglutide)
- [Orforglipron 0.8–17.2 mg](https://pepvault.app/peptides/orforglipron)
- [Survodutide 0.3–6 mg](https://pepvault.app/peptides/survodutide)
- [Mazdutide 2–6 mg](https://pepvault.app/peptides/mazdutide)
- [Pemvidutide 1.2–2.4 mg](https://pepvault.app/peptides/pemvidutide)

## Free tools

- [Retatrutide dose guide](https://pepvault.app/lab/dosage/retatrutide)
- [Reconstitution Lab (3D)](https://pepvault.app/lab)
- [Injection guide (3D)](https://pepvault.app/lab/injection)
- [Peptide Sky (3D)](https://pepvault.app/lab/sky)
- [Peptide tier list](https://pepvault.app/lab/tiers)
- [Reconstitution calculator](https://pepvault.app/tools/reconstitution-calculator)
- [Half-life & active level](https://pepvault.app/tools/peptide-half-life-calculator)
- [GLP-1 titration planner](https://pepvault.app/tools/glp1-titration-calculator)

Track your progress

## Watch it *work.*

Weight, waist and photos in one arc.

[Download on the App Store](https://apps.apple.com/app/apple-store/id6779318649?ppid=616838ec-3248-400f-bd58-4b93f85f1a20&pt=129020030&ct=peptides-progress-band&mt=8)

**34.8 lbs** down since June

Model. Individual results vary.

PepVault for iPhone

## Track Retatrutide in PepVault

Log every dose, keep your vial and the doses left in it and watch its estimated active level. 7 days free on the yearly plan for new subscribers.

[Download on the App Store](https://apps.apple.com/app/apple-store/id6779318649?ppid=616838ec-3248-400f-bd58-4b93f85f1a20&pt=129020030&ct=peptides-cta&mt=8)

[Open the calculator](https://pepvault.app/tools/reconstitution-calculator) [How the vial count works](https://pepvault.app/peptide-vial-tracker-app) [Explore the live demo](https://pepvault.app/login)

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

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.

© 2026 PepVault