---
title: "Retatrutide (LY3437943): Triple Agonist, Phase 2 Trial Data"
url: https://www.bodyhackguide.co/compound/retatrutide
description: "Retatrutide is a triple GLP-1/GIP/glucagon agonist by Eli Lilly. Phase 2 trial showed up to 24.2% weight loss at 48 weeks. Compare vendor prices, protocols"
lang: en
---

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# Retatrutide

Metabolic & Weight Loss (https://www.bodyhackguide.co/wiki#cat-metabolic-&-weight-loss)Phase 3

Also known as: Triple Agonist, GLP-3, 4x Blend, RC-3R, PEP-3R, GLP-3 RT, GLP-R, Ion Peptide Retatrutide, GIP/GLP/Glucagon, ION-3R, GLP-3R, Retatrutide, Reta, BHG-3R, BHG-3

Retatrutide (also coded LY3437943) is an investigational once-weekly triple-agonist at the GLP-1, GIP, and glucagon receptors. It is the third-generation incretin-based therapy developed by Eli Lilly.

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Half-life: ~6 days (plasma, albumin-bound) Route: subcutaneous MW: 4731 g/mol CAS: 2381294-46-4 135 PubMed results (https://pubmed.ncbi.nlm.nih.gov/?term=retatrutide%20LY3437943)

Last reviewed: May 4, 2026

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## Overview

### At A Glance

Mechanism

Retatrutide is a 39-amino-acid synthetic peptide with balanced agonist activity at three receptors: GLP-1R, GIPR, and GCGR (glucagon receptor). It is chemically modified with a C20 fatty diacid side chain (similar to semaglutide) to bind albumin and extend its plasma half-life to…

Half-Life

~6 days (plasma, albumin-bound)

Dosing

Once weekly subcutaneous injection

Dose Range

1,000–12,000 mcg (1–12 mg) per week

Routes

subcutaneous

Common Vials

5mg 10mg

Potential Benefits

Body weight reduction up to 24% at 48 weeks (Phase 2 data) Glycemic control in T2DM: HbA1c reduction similar to tirzepatide Hepatic fat reduction: potential MASH/NAFLD therapeutic effect Modest increase in resting energy expenditure (3-5%) Preferential visceral fat reduction Blood pressure and lipid profile improvement (secondary to weight loss) Once-weekly dosing convenience Average weight loss of 28.3% at 80 weeks on 12 mg in the Phase 3 TRIUMPH-1 trial (Eli Lilly topline)

Safety Notes

Common

Nausea Vomiting Diarrhea Constipation Decreased appetite

### Mechanism of Action

Retatrutide is a **39-amino-acid synthetic peptide with balanced agonist activity at three receptors**: GLP-1R, GIPR, and GCGR (glucagon receptor). It is chemically modified with a C20 fatty diacid side chain (similar to semaglutide) to bind albumin and extend its plasma half-life to ~6 days, enabling once-weekly subcutaneous dosing.

**1. GLP-1 receptor agonism (Gs / cAMP pathway on pancreatic beta cells and CNS)**

- Activates GLP-1R on pancreatic β-cells → glucose-dependent insulin secretion
- Activates GLP-1R on hypothalamic POMC/NPY/AgRP neurons → appetite suppression
- Slows gastric emptying → reduced postprandial glucose excursion and prolonged satiety
- Same mechanism as semaglutide, tirzepatide, liraglutide

EC₅₀ at human GLP-1R is roughly comparable to semaglutide.

**2. GIP receptor agonism (Gs / cAMP pathway on pancreatic beta cells and adipose tissue)**

- Activates GIPR on pancreatic β-cells → enhanced glucose-dependent insulin secretion
- Activates GIPR on adipose tissue → complex effects on lipid storage and energy expenditure
- Adds to GLP-1 effect on insulin secretion and satiety
- Same "twincretin" mechanism as tirzepatide

EC₅₀ at GIPR is comparable to tirzepatide.

**3. Glucagon receptor agonism — the retatrutide signature (Gs / cAMP pathway on hepatocytes and adipose tissue)**

This is what distinguishes retatrutide from semaglutide and tirzepatide:

- Activates GCGR on **hepatocytes** → hepatic glucose output (transient, requires β-cell compensation)
- Activates GCGR on hepatocytes → **stimulation of hepatic fatty acid oxidation** and reduction of hepatic lipid accumulation (the likely mechanism for retatrutide's strong NAFLD effects)
- Activates GCGR on **adipose tissue** → enhanced lipolysis and energy expenditure (measurable ~3-5% increase in resting metabolic rate in Phase 2)
- Activates GCGR in hypothalamus → additional appetite-suppressive effects

The glucagon component is the **reason retatrutide produces greater weight loss than GLP-1 + GIP alone**. Glucagon drives both direct lipolysis and increased energy expenditure, adding to the appetite-suppressive effect of GLP-1/GIP. The net calculus:

| Effect | GLP-1 (semaglutide) | GLP-1 + GIP (tirzepatide) | GLP-1 + GIP + GCG (retatrutide) |
| --- | --- | --- | --- |
| Appetite suppression | Strong | Strong+ | Strong++ |
| Insulin secretion | Enhanced | Enhanced+ | Enhanced+ |
| Gastric emptying delay | Strong | Strong | Strong |
| Lipolysis | Indirect (via caloric deficit) | Modest direct effect | **Strong direct effect** |
| Energy expenditure | Neutral | Slight increase | **+3-5% REE** |
| Hepatic fat reduction | Modest | Moderate | **Strong** |

**4. Balanced agonist design**

Retatrutide is designed as a **balanced triple agonist** — relative potencies at GLP-1R, GIPR, and GCGR are within one order of magnitude of each other. This is in contrast to earlier experimental triple agonists that were biased toward one receptor. The balance enables the clinical profile observed in Phase 2.

**5. Pharmacokinetics**

- Plasma half-life: ~6 days (albumin-binding via C20 fatty diacid)
- Steady state: achieved at ~4 weeks of weekly dosing
- Dosing: once-weekly subcutaneous injection
- Distribution: extensive albumin binding; moderate CNS penetration (enough for appetite-suppressive central effects)
- Clearance: predominantly hepatic; minimal renal excretion

Characterized in Phase 1 by [Urva et al., 2022].

**6. Secondary mechanisms under investigation**

- **Brown adipose tissue activation** — glucagon agonism likely activates BAT; may contribute to the energy expenditure increase
- **CNS energy-sensing neurons** — GLP-1/GIP/GCG all signal at hypothalamic energy-sensing neurons; triple activation may produce qualitatively different satiety signaling than GLP-1 alone

### Overview

Retatrutide (also coded **LY3437943**) is an **investigational once-weekly triple-agonist** at the **GLP-1, GIP, and glucagon receptors**. It is the third-generation incretin-based therapy developed by Eli Lilly. Where Semaglutide (https://www.bodyhackguide.co/compound/semaglutide) activates GLP-1 alone and Tirzepatide (https://www.bodyhackguide.co/compound/tirzepatide) activates both GLP-1 and GIP, retatrutide adds glucagon receptor agonism for synergistic effects on energy expenditure, hepatic lipid metabolism, and weight reduction.

As of September 2026, retatrutide is **not FDA-approved**. Its Phase 3 program covers obesity (the TRIUMPH trials), type 2 diabetes (the TRANSCEND-T2D trials), fatty liver disease, and cardiovascular and kidney outcomes. In the lead obesity trial, TRIUMPH-1, the 12 mg dose produced 28.3% average weight loss at 80 weeks (Eli Lilly topline, May 2026).

The clinical excitement around retatrutide is driven by the Phase 2 obesity trial data published in NEJM in 2023: participants on retatrutide 12 mg weekly achieved **24.2% body weight reduction at 48 weeks**, more than the main trials of semaglutide (~15% at 68 weeks in STEP-1) and tirzepatide (~21% at 72 weeks in SURMOUNT-1) had shown ([Jastreboff et al., 2023]).

Despite the strong efficacy signal, retatrutide's triple-receptor profile carries **distinct safety considerations** beyond the GLP-1 class:

- **Heart rate elevation**: mean ~6-8 bpm increase (larger than semaglutide or tirzepatide), likely driven by the glucagon-receptor component
- **Transient elevation of fasting glucose** during uptitration (glucagon receptor effect on hepatic glucose output), usually self-limited
- **Higher rate of GI adverse events** at the 12 mg maximal dose compared to lower doses and compared to GLP-1-only agents
- **Unknown long-term cardiovascular outcomes**: the large Phase 3 cardiovascular and kidney outcomes trial, TRIUMPH-Outcomes, is still running

**Regulatory status:** Not FDA-approved. Available only through clinical trials, Eli Lilly's pre-approval expanded access program (requested by a physician, for adults with a BMI of 35 or more and serious obesity-related complications who have run out of approved options and cannot join a trial), research-chemical channels, and (controversially) compounding pharmacies in some jurisdictions using non-commercial retatrutide sourcing. Eli Lilly plans to submit it to the FDA in the first quarter of 2027.

Typical dosing (extrapolated from Phase 2 uptitration schedule): **starting 2 mg weekly SC, titrating to 8-12 mg weekly over 12-20 weeks**. The maximal dose of 12 mg weekly is associated with the largest weight loss and the largest side-effect burden. See our Retatrutide Dosage Guide (https://www.bodyhackguide.co/guides/dosage/retatrutide) for uptitration specifics and our Semaglutide vs Tirzepatide vs Retatrutide (https://www.bodyhackguide.co/blog/glp1-comparison-2026) comparison for class-selection context.

### Potential Research Fields

Obesity Type 2 diabetes Metabolic syndrome NASH

### Phase 2 Trial Data: Weight Loss Results

Eli Lilly's Phase 2 trial (n=338, published in _NEJM_ 2023) tested retatrutide at doses from 1mg to 12mg weekly over 48 weeks in adults with obesity (BMI ≥30) or overweight (BMI ≥27) with at least one weight-related condition.

24.2%

Mean weight loss at 12mg (48 wk)

26%

12mg group losing ≥30% BW (48 wk)

86%

Liver fat cut at 12mg (48 wk)

#### Dose-Response Weight Loss at 48 Weeks (low/high = 2 mg or 4 mg starting dose)

1 mg

-8.7%

4 mg (low)

-16.3%

4 mg (high)

-17.8%

8 mg (low)

-21.7%

8 mg (high)

-23.9%

12 mg

-24.2%

**Phase 3:** TRIUMPH-1 reported 28.3% average weight loss at 80 weeks on the 12 mg dose (May 2026), and TRIUMPH-2 and TRIUMPH-3 also met their primary endpoints (July 2026). Eli Lilly plans to submit retatrutide to the FDA in Q1 2027.

### Triple Agonism: Why 3 Receptors Matter

#### GLP-1 Receptor

Suppresses appetite, enhances insulin secretion, slows gastric emptying. Same pathway as semaglutide.

#### GIP Receptor

Modulates lipid metabolism and adipose tissue function. Combined with GLP-1 in tirzepatide.

#### Glucagon Receptor

Key differentiator from semaglutide and tirzepatide. Drives hepatic fat oxidation and can raise energy expenditure (animal models and short human glucagon studies).

### Retatrutide vs Tirzepatide vs Semaglutide

| Compound | Targets | Max Weight Loss | Trial | Status |
| --- | --- | --- | --- | --- |
| Semaglutide | GLP-1 | ~15% | STEP-1 (68 wk) | FDA Approved |
| Tirzepatide | GLP-1 + GIP | ~22.5% | SURMOUNT-1 (72 wk) | FDA Approved |
| Retatrutidebest | GLP-1 + GIP + Glucagon | ~28.3% | TRIUMPH-1 (80 wk) | Phase 3 |

Cross-trial comparisons: interpret with caution due to study population differences.

### Phase 2 Titration Schedule

Weeks 1-2 1 mg/week Starting dose

Weeks 3-4 2 mg/week First escalation

Weeks 5-8 4 mg/week Intermediate dose

Weeks 9-12 8 mg/week High dose

Weeks 13-48 12 mg/week Maximum (if tolerated)

**Do not skip titration.** Jumping to high doses significantly increases GI side effects. If intolerable, stay at current dose for 2 extra weeks before escalating.

### Detailed Side Effects

#### Common (≥10%)

- • Nausea (dose-dependent, usually improves)
- • Diarrhea
- • Constipation
- • Decreased appetite
- • Vomiting (mostly during titration)

#### Less Common

- • Increased heart rate
- • Injection site reactions
- • Fatigue
- • Dizziness
- • Dysesthesia (abnormal skin sensations, dose-related)
- • Preclinical thyroid C-cell concerns

**Contraindications:** Do NOT combine with semaglutide, tirzepatide, or other GLP-1 agonists. Avoid if personal/family history of medullary thyroid carcinoma or MEN2.

### Retatrutide FAQ

What is retatrutide (LY3437943)?

Retatrutide is an investigational triple hormone receptor agonist developed by Eli Lilly that simultaneously activates GLP-1, GIP, and glucagon receptors. It produced up to 24.2% weight loss at 48 weeks in Phase 2 and 28.3% at 80 weeks in the Phase 3 TRIUMPH-1 trial.

How does retatrutide differ from tirzepatide and semaglutide?

Semaglutide targets GLP-1 only. Tirzepatide targets GLP-1 + GIP (dual agonist). Retatrutide targets GLP-1 + GIP + glucagon (triple agonist). The glucagon receptor activation drives hepatic fat oxidation and can raise energy expenditure (shown in animal models and in short human glucagon studies, not yet published for retatrutide itself), mechanisms that neither semaglutide nor tirzepatide has.

What were the retatrutide Phase 2 trial results?

The Phase 2 trial (n=338) showed up to 24.2% mean body weight reduction with the 12mg dose at 48 weeks: 83% of that group lost at least 15% of their body weight and 26% lost 30% or more. In the trial's liver-fat substudy (98 participants with at least 10% liver fat), the 12mg dose cut liver fat by 86% at 48 weeks. The timepoints do not line up with the other trials: semaglutide's 14.9% came at 68 weeks in STEP-1 and tirzepatide's 22.5% at 72 weeks in SURMOUNT-1.

What are retatrutide's side effects?

Common side effects include nausea, vomiting, diarrhea, constipation, and decreased appetite, similar to other GLP-1 agonists. Additional effects include increased heart rate, injection site reactions, fatigue, and dysesthesia (unpleasant abnormal skin sensations), which the Phase 3 trials reported in 4.4% to 20.9% of people on 12 mg against 0% to 1.3% on placebo. Preclinical thyroid concerns have been noted. Most GI side effects were dose-dependent and improved with titration.

What is the retatrutide dosing protocol?

Per the Phase 2 trial protocol: start at 1mg subcutaneous once weekly for 2 weeks, then titrate up through 2mg, 4mg, 8mg, and potentially 12mg over 24 weeks. The ~6-day half-life supports weekly dosing. Slow titration minimizes GI side effects.

Is retatrutide FDA approved?

No. Retatrutide is still investigational. Four of its Phase 3 TRIUMPH obesity trials have reported: TRIUMPH-4 in December 2025, TRIUMPH-1 in May 2026, TRIUMPH-2 and TRIUMPH-3 in July 2026. Others are still running, including TRIUMPH-5 against tirzepatide. Eli Lilly plans to submit it to the FDA in the first quarter of 2027, so any approval would come after that review. Outside those trials and Lilly's pre-approval expanded access program for severe obesity, it is available only as a research compound.

Can I stack retatrutide with semaglutide or tirzepatide?

No. Retatrutide already includes GLP-1 agonism. Stacking with semaglutide or tirzepatide would produce dangerous overlapping GLP-1 activity and is strongly contraindicated.

## Chemical Information

IUPAC Name

Not fully disclosed (Eli Lilly proprietary)

CAS Number

2381294-46-4

Molecular Formula

C221H342N46O68

Molecular Mass

4731 g/mol

Image: Retatrutide molecular structure (https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/171390338/PNG?image_size=300x300)

View on PubChem: https://pubchem.ncbi.nlm.nih.gov/compound/171390338

Amino Acid Sequence

39-amino-acid synthetic peptide; GIP/GLP-1/glucagon triple receptor agonist (Eli Lilly LY3437943; CAS 2381089-83-2). Backbone (N->C, one-letter): YAQGTFTSDYSILLDKKAQAAFIEYLLEGGPSSGAPPPS. Key modifications (per the published structure): 2-aminoisobutyric acid (Aib) at positions 2 and 20; a C20 fatty diacid conjugated to a lysine side chain via a gamma-Glu/AEEA linker (albumin-binding moiety that extends the plasma half-life to ~6 days); C-terminal amidation. Molecular formula C221H342N46O68; molecular weight ~4731 g/mol.

## Dosing & Protocols

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## Research

### Unlock the research summary

- A summary of the key research
- Safety and side effects
- A link to the PubMed results

## Interactions

### Interaction Matrix

### Contraindications

**Absolute contraindications**

- **Personal or family history of medullary thyroid carcinoma (MTC)** — GLP-1 class rodent carcinogenicity signal; absolute contraindication
- **Multiple Endocrine Neoplasia syndrome type 2 (MEN-2)** — same signal
- **History of acute pancreatitis** — GLP-1 class signal; recurrence risk
- **Active gallbladder disease / acute cholecystitis** — GLP-1 class worsens
- **Active malignancy** — relative to absolute depending on type; GLP-1 class has some residual oncology concerns
- **Pregnancy or planning pregnancy** — no safety data; avoid
- **Breastfeeding** — no safety data
- **Age <18** — no pediatric data for retatrutide (some GLP-1 class drugs have pediatric obesity approvals; retatrutide does not)
- **Severe gastroparesis or gastric outlet obstruction** — GLP-1 mechanism would dramatically worsen

**Relative contraindications (consult physician before use)**

- **History of chronic pancreatitis** — increased recurrence risk
- **Active proliferative diabetic retinopathy** — rapid glycemic correction can worsen retinopathy
- **Resting tachycardia (HR >90 at baseline)** — retatrutide consistently raises HR; investigate baseline cause first
- **Severe heart failure (NYHA III-IV)** — limited data; the heart rate elevation may be problematic
- **Active eating disorder (anorexia nervosa / bulimia)** — appetite suppression is dangerous
- **Severe hepatic impairment (Child-Pugh C)** — hepatic clearance is primary
- **Severe chronic kidney disease (eGFR <30)** — limited data

**Drug interactions**

- **Sulfonylureas (glipizide, glyburide)** — hypoglycemia risk; reduce dose 50% when starting retatrutide
- **Insulin** — hypoglycemia risk; reduce insulin dose at retatrutide initiation
- **Other GLP-1 receptor agonists** — redundant; discontinue before starting retatrutide
- **Warfarin** — GLP-1 class may alter INR; monitor more frequently at dose changes
- **Oral contraceptives** — GLP-1-induced gastric delay may reduce efficacy; consider non-oral contraception during active uptitration
- **Acetaminophen / paracetamol** — gastric delay may reduce Cmax; usually not clinically significant
- **Any drug with narrow therapeutic index requiring predictable absorption** — monitor at dose changes

**Specific populations requiring extra caution**

- **History of depression / suicidal ideation** — some GLP-1 class drugs have FDA adverse event signals for suicidality; monitor
- **History of retinopathy** — annual ophthalmology during rapid weight loss
- **Post-bariatric surgery** — limited data on GLP-1 class post-surgery; absorption may be altered

**Monitoring requirements**

- **Baseline:** HbA1c, fasting glucose, lipid panel, CMP, liver function, thyroid (TSH + free T4), blood pressure, resting heart rate (seated, post-rest), pregnancy test (women of childbearing age), eye exam (for diabetics or high-risk)
- **Every 4 weeks during uptitration:** fasting glucose, blood pressure, heart rate, weight, subjective tolerance
- **Every 12 weeks on maintenance:** HbA1c, liver function, lipids, weight, body composition
- **Annually:** Full panel + cardiovascular assessment + ophthalmology (if diabetic)

**Discontinuation criteria**

Stop retatrutide and consult a clinician if you develop:

- Severe persistent GI symptoms limiting food intake
- Any suspected pancreatitis symptoms (severe abdominal pain radiating to back)
- Severe hypoglycemia (glucose <54 mg/dL)
- Resting HR >100 bpm or new arrhythmia
- Severe depression or suicidal ideation
- Acute gallbladder symptoms
- Unexplained dehydration or electrolyte derangement
- Planning pregnancy

Research Disclaimer

This interaction data is compiled from published research and community reports. It may not be exhaustive. Always consult a healthcare professional before combining compounds.

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### Vendors Selling Retatrutide

#### VANDL Labs

4 listings · from $79.99
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#### BioMyst Labs

4.5

4 listings · from $99.99
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### AOD-9604

Metabolic & Weight Loss Phase 3

AOD-9604 (Anti-Obesity Drug 9604) is a synthetic 16-amino-acid peptide fragment of human growth hormone (hGH) corresponding to residues 177-191 of the hGH molecule plus a tyrosine addition at the N-terminus (sequence: Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe).

t½ ~30–60 minutes 250–600 mcg per injection

1 PubMed View Profile
https://www.bodyhackguide.co/compound/aod-9604

### ATX-304

Metabolic & Weight Loss Phase IIa Clinical Trials

ATX-304 (also known as O-304) is an orally bioavailable, first-in-class pan-AMPK activator with a mild mitochondrial-uncoupling effect.

Preclinical View Profile
https://www.bodyhackguide.co/compound/atx-304

### Cagrilintide

Metabolic & Weight Loss Phase 3

Cagrilintide (also known as AM833, development code NN9838) is a long-acting amylin analog developed by Novo Nordisk as a next-generation weight-management therapy, designed to be co-administered with the GLP-1 receptor agonist semaglutide in a fixed-ratio combination known as CagriSema.

t½ ~159 hours (approximately 7 days)

46 PubMed View Profile
https://www.bodyhackguide.co/compound/cagrilintide

### HGH Fragment 176-191

Metabolic & Weight Loss Phase 2

HGH Fragment 176-191 (also written HGH Frag 176-191, hGH Fragment 176-191, and frequently appearing in clinical literature as AOD-9604 — "Anti-Obesity Drug 9604") is a synthetic peptide corresponding to the C-terminal 15-amino-acid region of the 191-amino-acid human growth hormone (hGH) molecule, with an additional N-terminal tyrosine residue added for stability and biological activity.

t½ ~30 minutes (short plasma half-life) 250-500 mcg

2 PubMed View Profile
https://www.bodyhackguide.co/compound/hgh-frag-176-191

### Semaglutide

Metabolic & Weight Loss FDA Approved

Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with a molecular weight of 4113.58 Da and CAS number 910463-68-2.

t½ ~7 days (168 hours), enabled by C18 fatty diacid albumin-binding modification Diabetes (Ozempic): 250-1000 mcg weekly; Weight management (Wegovy): 2400 mcg weekly (after 16-week titration); Oral (Rybelsus): 3-14 mg daily

3,273 PubMed View Profile
https://www.bodyhackguide.co/compound/semaglutide

### Tirzepatide

Metabolic & Weight Loss FDA Approved

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist with a molecular weight of 4813.45 Da and CAS number 2023788-19-2.

t½ ~5 days (approximately 120 hours), enabled by C20 fatty diacid albumin-binding modification 2500 mcg (2.5 mg) starting dose, titrated every 4 weeks through 5000, 7500, 10000, 12500, to 15000 mcg (15 mg) maximum weekly dose

626 PubMed View Profile
https://www.bodyhackguide.co/compound/tirzepatide

### Side-by-Side Comparisons

All Comparisons (https://www.bodyhackguide.co/compare)

Retatrutide vs Tirzepatide: https://www.bodyhackguide.co/compare/retatrutide-vs-tirzepatide
Retatrutide vs Semaglutide: https://www.bodyhackguide.co/compare/retatrutide-vs-semaglutide

View Full Dosage Guide →

Protocols, calculator & safety for Retatrutide
https://www.bodyhackguide.co/guides/dosage/retatrutide

### Related Articles

All Posts (https://www.bodyhackguide.co/blog)

#### The 8 Best Peptide Companies for Research: 2026 Purity & Price Comparison

A data-driven comparison of every active peptide vendor we track: COA audit results, price-per-mg tables for 19 compounds, and a step-by-step purchase guide.

9/16/2026
https://www.bodyhackguide.co/blog/best-peptide-companies-2026

#### Tesamorelin: A Complete Research Reference

Tesamorelin is a synthetic, stabilized GHRH analog approved as Egrifta for HIV-associated visceral fat. This guide covers the real trial evidence for visceral fat, liver fat, and cognition, how it differs from CJC-1295 and from GH itself, the approved and studied doses, and how the peptide-research community discusses it, with research-use-only framing throughout.

7/1/2026
https://www.bodyhackguide.co/blog/tesamorelin-research-guide

#### Aquasome Nanotechnology and Oral Peptides: The Mechanism, the Research, and the 10 Compounds It Actually Works For

how aquasome 3-layer nano-encapsulation lets peptides like retatrutide, bpc-157, and tb-500 survive the gut. pubmed-backed deep dive on the 10 compounds it works for.

5/20/2026
https://www.bodyhackguide.co/blog/aqasome-nanotechnology-oral-peptides

### Featured Price

⚗️

ResearchChemHQ

$119.99($12.00/mg)

5 vendors · 11 listings

### Research Score

74

135 PubMed results

### Quality Indicators

Data Completeness

100%

Description

Mechanism of Action

Chemical Data

Dosing Protocols

Safety Profile

PubMed Results

Interactions

Vendor Listings

COA Verification

10

Verified COAs

2

Vendors w/ COA

High verification rate (83%)

Latest test: 3/1/2026

Research Volume

135 PubMed results

Well-researched compound

### Quick Facts

Half-Life

~6 days (plasma, albumin-bound)

Molecular Weight

4731 g/mol

Administration

subcutaneous

CAS Number

2381294-46-4

Trial Phase

Phase 3

### Safety Profile

Moderate Risk

Common Side Effects

- • Nausea
- • Vomiting
- • Diarrhea
- • Constipation
- • Decreased appetite

Stop Use If

- Long-term safety profile still being established; Phase 3 trials are still running
- Thyroid tumor history
- Severe GI events

Research Disclaimer

This information is for educational and research purposes only. Not intended as medical advice. Consult a healthcare professional before use.

## Frequently Asked Questions

What is retatrutide (LY3437943)?

What are retatrutide's side effects?

Is retatrutide FDA approved?

## Research Tools

### Peptide Calculator

Reconstitution & syringe units
https://www.bodyhackguide.co/tools/reconstitution

### Reconstitution Guide

How to mix, step by step
https://www.bodyhackguide.co/guides/how-to-reconstitute-peptides

### Nasal Spray Calc

mL per actuation
https://www.bodyhackguide.co/tools/intranasal

### Half-Life Visualizer

Decay curves
https://www.bodyhackguide.co/tools/halflife

## Related Compounds

### AOD-9604

Metabolic & Weight Loss Phase 3

### ATX-304

### Cagrilintide

Metabolic & Weight Loss Phase 3

t½ ~159 hours (approximately 7 days)

### HGH Fragment 176-191

Metabolic & Weight Loss Phase 2

### Semaglutide

Metabolic & Weight Loss FDA Approved

### Tirzepatide

Metabolic & Weight Loss FDA Approved

## Side-by-Side Comparisons

Compare Retatrutide head-to-head: mechanism, half-life, dosing, safety, and vendor prices.

Free 2026 Peptide Cheat Sheet (PDF)

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Download Free (https://www.bodyhackguide.co/guides/peptide-cheat-sheet-download)

### Need bloodwork before starting?

Full hormone + metabolic panels from Anabolic Insights. Code CHONCH for first-order discount.

Image: BodyHackGuide (https://www.bodyhackguide.co/assets/bodyhackguide-logo-DOzZNUyh.webp)

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Your biohacking research hub: compound pricing, brain health protocols, dosing tools, and vendor reviews.

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**Research Disclaimer:** All compounds listed are for laboratory and research purposes only. Not for human consumption. This site does not sell or ship any products. Always consult a qualified healthcare professional and comply with local regulations.

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      "description": "Retatrutide (also coded LY3437943) is an investigational once-weekly triple-agonist at the GLP-1, GIP, and glucagon receptors. It is the third-generation incretin-based therapy developed by Eli Lilly. Where Semaglutide activates GLP-1 alone and Tirzepatide activates both GLP-1 and GIP, retatrutide adds glucagon receptor agonism for synergistic effects on energy expenditure, hepatic lipid metabolism, and weight reduction. As of September 2026, retatrutide is not FDA-approved. Its Phase 3 program covers obesity (the TRIUMPH trials), type 2 diabetes (the TRANSCEND-T2D trials), fatty liver disease, and cardiovascular and kidney outcomes. In the lead obesity trial, TRIUMPH-1, the 12 mg dose produced 28.3% average weight loss at 80 weeks (Eli Lilly topline, May 2026). The clinical excitement around retatrutide is driven by the Phase 2 obesity trial data published in NEJM in 2023: participants on retatrutide 12 mg weekly achieved 24.2% body weight reduction at 48 weeks, more than the main trials of semaglutide (~15% at 68 weeks in STEP-1) and tirzepatide (~21% at 72 weeks in SURMOUNT-1) had shown ([Jastreboff et al., 2023]). Despite the strong efficacy signal, retatrutide's triple-receptor profile carries distinct safety considerations beyond the GLP-1 class: Heart rate elevation: mean ~6-8 bpm increase (larger than semaglutide or tirzepatide), likely driven by the glucagon-receptor component Transient elevation of fasting glucose during uptitration (glucagon receptor effect on hepatic glucose output), usually self-limited Higher rate of GI adverse events at the 12 mg maximal dose compared to lower doses and compared to GLP-1-only agents Unknown long-term cardiovascular outcomes: the large Phase 3 cardiovascular and kidney outcomes trial, TRIUMPH-Outcomes, is still running Regulatory status: Not FDA-approved. Available only through clinical trials, Eli Lilly's pre-approval expanded access program (requested by a physician, for adults with a BMI of 35 or more and serious obesity-related complications who have run out of approved options and cannot join a trial), research-chemical channels, and (controversially) compounding pharmacies in some jurisdictions using non-commercial retatrutide sourcing. Eli Lilly plans to submit it to the FDA in the first quarter of 2027. Typical dosing (extrapolated from Phase 2 uptitration schedule): starting 2 mg weekly SC, titrating to 8-12 mg weekly over 12-20 weeks. The maximal dose of 12 mg weekly is associated with the largest weight loss and the largest side-effect burden. See our Retatrutide Dosage Guide for uptitration specifics and our Semaglutide vs Tirzepatide vs Retatrutide comparison for class-selection context.",
      "activeIngredient": "Retatrutide",
      "administrationRoute": "subcutaneous",
      "mechanismOfAction": "Retatrutide is a 39-amino-acid synthetic peptide with balanced agonist activity at three receptors: GLP-1R, GIPR, and GCGR (glucagon receptor). It is chemically modified with a C20 fatty diacid side chain (similar to semaglutide) to bind albumin and extend its plasma half-life to ~6 days, enabling once-weekly subcutaneous dosing. GLP-1 receptor agonism (Gs / cAMP pathway on pancreatic beta cells and CNS) Activates GLP-1R on pancreatic β-cells → glucose-dependent insulin secretion Activates GLP-1R on hypothalamic POMC/NPY/AgRP neurons → appetite suppression Slows gastric emptying → reduced postprandial glucose excursion and prolonged satiety Same mechanism as semaglutide, tirzepatide, liraglutide EC₅₀ at human GLP-1R is roughly comparable to semaglutide. GIP receptor agonism (Gs / cAMP pathway on pancreatic beta cells and adipose tissue) Activates GIPR on pancreatic β-cells → enhanced glucose-dependent insulin secretion Activates GIPR on adipose tissue → complex effects on lipid storage and energy expenditure Adds to GLP-1 effect on insulin secretion and satiety Same \"twincretin\" mechanism as tirzepatide EC₅₀ at GIPR is comparable to tirzepatide. Glucagon receptor agonism — the retatrutide signature (Gs / cAMP pathway on hepatocytes and adipose tissue) This is what distinguishes retatrutide from semaglutide and tirzepatide: Activates GCGR on hepatocytes → hepatic glucose output (transient, requires β-cell compensation) Activates GCGR on hepatocytes → stimulation of hepatic fatty acid oxidation and reduction of hepatic lipid accumulation (the likely mechanism for retatrutide's strong NAFLD effects) Activates GCGR on adipose tissue → enhanced lipolysis and energy expenditure (measurable ~3-5% increase in resting metabolic rate in Phase 2) Activates GCGR in hypothalamus → additional appetite-suppressive effects The glucagon component is the reason retatrutide produces greater weight loss than GLP-1 + GIP alone. Glucagon drives both direct lipolysis and increased energy expenditure, adding to the appetite-suppressive effect of GLP-1/GIP. The net calculus: Balanced agonist design Retatrutide is designed as a balanced triple agonist — relative potencies at GLP-1R, GIPR, and GCGR are within one order of magnitude of each other. This is in contrast to earlier experimental triple agonists that were biased toward one receptor. The balance enables the clinical profile observed in Phase 2. Pharmacokinetics Plasma half-life: ~6 days (albumin-binding via C20 fatty diacid) Steady state: achieved at ~4 weeks of weekly dosing Dosing: once-weekly subcutaneous injection Distribution: extensive albumin binding; moderate CNS penetration (enough for appetite-suppressive central effects) Clearance: predominantly hepatic; minimal renal excretion Characterized in Phase 1 by [Urva et al., 2022]. Secondary mechanisms under investigation Brown adipose tissue activation — glucagon agonism likely activates BAT; may contribute to the energy expenditure increase CNS energy-sensing neurons — GLP-1/GIP/GCG all signal at hypothalamic energy-sensing neurons; triple activation may produce qualitatively different satiety signaling than GLP-1 alone",
      "dosageForm": "vial",
      "legalStatus": "Not approved for human use (research chemical)",
      "warning": "For research purposes only. Not for human consumption."
    }
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      {
        "@type": "Question",
        "name": "What is retatrutide (LY3437943)?",
        "acceptedAnswer": {
          "@type": "Answer",
          "text": "Retatrutide is an investigational triple hormone receptor agonist developed by Eli Lilly that simultaneously activates GLP-1, GIP, and glucagon receptors. It produced up to 24.2% weight loss at 48 weeks in Phase 2 and 28.3% at 80 weeks in the Phase 3 TRIUMPH-1 trial."
        }
      },
      {
        "@type": "Question",
        "name": "How does retatrutide differ from tirzepatide and semaglutide?",
        "acceptedAnswer": {
          "@type": "Answer",
          "text": "Semaglutide targets GLP-1 only. Tirzepatide targets GLP-1 + GIP (dual agonist). Retatrutide targets GLP-1 + GIP + glucagon (triple agonist). The glucagon receptor activation drives hepatic fat oxidation and can raise energy expenditure (shown in animal models and in short human glucagon studies, not yet published for retatrutide itself), mechanisms that neither semaglutide nor tirzepatide has."
        }
      },
      {
        "@type": "Question",
        "name": "What were the retatrutide Phase 2 trial results?",
        "acceptedAnswer": {
          "@type": "Answer",
          "text": "The Phase 2 trial (n=338) showed up to 24.2% mean body weight reduction with the 12mg dose at 48 weeks: 83% of that group lost at least 15% of their body weight and 26% lost 30% or more. In the trial's liver-fat substudy (98 participants with at least 10% liver fat), the 12mg dose cut liver fat by 86% at 48 weeks. The timepoints do not line up with the other trials: semaglutide's 14.9% came at 68 weeks in STEP-1 and tirzepatide's 22.5% at 72 weeks in SURMOUNT-1."
        }
      },
      {
        "@type": "Question",
        "name": "What are retatrutide's side effects?",
        "acceptedAnswer": {
          "@type": "Answer",
          "text": "Common side effects include nausea, vomiting, diarrhea, constipation, and decreased appetite, similar to other GLP-1 agonists. Additional effects include increased heart rate, injection site reactions, fatigue, and dysesthesia (unpleasant abnormal skin sensations), which the Phase 3 trials reported in 4.4% to 20.9% of people on 12 mg against 0% to 1.3% on placebo. Preclinical thyroid concerns have been noted. Most GI side effects were dose-dependent and improved with titration."
        }
      },
      {
        "@type": "Question",
        "name": "What is the retatrutide dosing protocol?",
        "acceptedAnswer": {
          "@type": "Answer",
          "text": "Per the Phase 2 trial protocol: start at 1mg subcutaneous once weekly for 2 weeks, then titrate up through 2mg, 4mg, 8mg, and potentially 12mg over 24 weeks. The ~6-day half-life supports weekly dosing. Slow titration minimizes GI side effects."
        }
      },
      {
        "@type": "Question",
        "name": "Is retatrutide FDA approved?",
        "acceptedAnswer": {
          "@type": "Answer",
          "text": "No. Retatrutide is still investigational. Four of its Phase 3 TRIUMPH obesity trials have reported: TRIUMPH-4 in December 2025, TRIUMPH-1 in May 2026, TRIUMPH-2 and TRIUMPH-3 in July 2026. Others are still running, including TRIUMPH-5 against tirzepatide. Eli Lilly plans to submit it to the FDA in the first quarter of 2027, so any approval would come after that review. Outside those trials and Lilly's pre-approval expanded access program for severe obesity, it is available only as a research compound."
        }
      },
      {
        "@type": "Question",
        "name": "Can I stack retatrutide with semaglutide or tirzepatide?",
        "acceptedAnswer": {
          "@type": "Answer",
          "text": "No. Retatrutide already includes GLP-1 agonism. Stacking with semaglutide or tirzepatide would produce dangerous overlapping GLP-1 activity and is strongly contraindicated."
        }
      }
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