GLP-1 Agonist Phase III

Retatrutide

Also known as: LY3437943, Reta

An investigational triple agonist targeting GIP, GLP-1, and glucagon receptors — produced record-breaking 24.2% weight loss in Phase 2 trials.

Popularity A+
Class Triple GIP/GLP-1/Glucagon Receptor Agonist
Half-Life ~6 days
Form Lyophilized powder (research), Pre-filled pen (clinical)
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Retatrutide C228H356N50O70
Research-Backed User Reports Sourced Updated Mar 2026
// Overview

What is Retatrutide?

Retatrutide (LY3437943) is an investigational triple hormone receptor agonist developed by Eli Lilly that targets GIP, GLP-1, and glucagon receptors simultaneously. It represents the next evolution beyond dual agonists like tirzepatide, adding glucagon receptor activity to further enhance metabolic effects.

In the Phase 2 trial published in the New England Journal of Medicine, retatrutide produced up to 24.2% body weight loss at the highest dose over 48 weeks — the largest weight reduction ever reported for any anti-obesity medication in a clinical trial. The triple-agonist approach addresses obesity from three distinct hormonal pathways.

The addition of glucagon receptor agonism increases energy expenditure and hepatic lipid oxidation, complementing the appetite-suppressing effects of GIP and GLP-1 activation. This mechanism also showed remarkable effects on liver fat reduction, with some patients achieving complete resolution of fatty liver disease.

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// How It Works

How Retatrutide Works

Retatrutide activates three metabolic hormone receptors simultaneously:

  1. GLP-1 receptor — Suppresses appetite, slows gastric emptying, and enhances glucose-dependent insulin secretion. This is the primary weight loss mechanism shared with semaglutide.
  2. GIP receptor — Amplifies insulin response, improves lipid metabolism, and may reduce the nausea associated with GLP-1 activation alone.
  3. Glucagon receptor — The novel third target. Increases hepatic fat oxidation, raises energy expenditure (thermogenesis), and promotes lipolysis. This mechanism drives the dramatic liver fat reduction seen in trials.

The triple-agonist approach produces greater weight loss and metabolic improvement than dual (tirzepatide) or single (semaglutide) agonists.

// Dosage Protocols

Dosage Information (User-Reported)

Disclaimer: Dosage information is compiled from user reports and published research. This is not medical advice. Consult a healthcare professional before use.
Level Dose Frequency Duration
Starter 0.5 mg Once weekly 4 weeks
Titration 1 2 mg Once weekly 4 weeks
Titration 2 4 mg Once weekly 4 weeks
Therapeutic Low 8 mg Once weekly Ongoing
Therapeutic High 12 mg Once weekly Ongoing

What to Expect

Week 1-4

Appetite reduction begins at low titration doses. GI effects similar to other GLP-1 drugs. Some users report increased body temperature from glucagon activity.

Week 5-12

Dramatic appetite suppression. Faster weight loss trajectory than semaglutide or tirzepatide at equivalent timepoints. Energy expenditure feels elevated.

Month 3-6

Substantial body recomposition. Users report 15-20%+ total weight loss. Liver enzyme normalization in those with elevated baselines.

Month 6-12

Weight loss continues toward 20-25% of starting body weight. Metabolic panels show broad improvement across glucose, lipids, and liver markers.

Common Stacks

BPC-157

GI Support

Helps manage nausea and gastric slowing from triple-agonist activity

L-Carnitine

Fat Metabolism

Supports increased fatty acid oxidation driven by glucagon receptor activation

Electrolytes / Magnesium

Hydration Support

Compensates for increased water loss and mineral depletion during rapid weight reduction

// Preparation

Reconstitution & Storage

Research-grade: Reconstitute with bacteriostatic water. Add water slowly, do not shake. Swirl gently until dissolved. Refrigerate and use within 21 days.

Storage: Refrigerate 2-8°C. Protect from light.

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// Safety Profile

Side Effects & Safety

Potential Side Effects

  • ! Nausea (most common during titration)
  • ! Diarrhea
  • ! Vomiting
  • ! Decreased appetite
  • ! Constipation
  • ! Increased heart rate
  • ! Injection site reactions
  • ! Elevated body temperature (glucagon effect)
  • ! Gallbladder events with rapid weight loss

Contraindications

  • ⚠ Personal or family history of medullary thyroid carcinoma
  • ⚠ MEN 2 syndrome
  • ⚠ Pregnancy or breastfeeding
  • ⚠ Active pancreatitis
  • ⚠ Severe hepatic or renal impairment

Legal & Regulatory Status

Investigational — not yet FDA-approved. Currently in Phase 3 clinical trials (TRIUMPH program) by Eli Lilly. Research-grade retatrutide available from select peptide vendors for research purposes only.

// Research

Published Research

// Where to Buy

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// Related Compounds

Other GLP-1 Agonist Guides

Cagrilintide

A long-acting amylin analog that amplifies weight loss when paired with semaglutide — the amylin component of CagriSema's…

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BPC-157 Arginate (Oral)

The oral form of BPC-157 — gastric-acid stable and designed for direct GI tract healing. No injections needed…

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TB-500 Fragment

A concentrated fragment of Thymosin Beta-4 focused on the core actin-binding domain — smaller molecule, targeted tissue repair.

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This content is for informational and educational purposes only. Retatrutide is sold for research purposes. Never Natty does not condone or encourage the use of any substance in violation of any laws. Consult a healthcare professional before using any compound discussed on this site.