Weight Management

Retatrutide

Retatrutide (Triple GIP/GLP-1/Glucagon Agonist)

The triple agonist showing 24% weight loss in trials

Retatrutide is a next-generation triple hormone receptor agonist (GIP, GLP-1, and glucagon) in Phase 3 clinical trials. Early data showed up to 24.2% body weight reduction - the most ever seen in a drug trial.

Retatrutide illustration

Admin routes

Subcutaneous

Popularity

Medium

Side effects

Generally mild

Vendors

2 rated

Key benefits

124.2% average weight loss at highest dose (Phase 2)
2Most potent weight loss agent ever tested in clinical trials
3Triple mechanism may better preserve metabolic rate
4Significant reduction in liver fat (relevant for NAFLD)
5Once-weekly dosing
6May produce less muscle wasting than GLP-1-only agonists

What to expect

1
Week 1–4

Significant appetite reduction; GI adjustment period

2
Week 4–12

Rapid weight loss phase; 6–10% body weight

3
Week 12–24

Continued weight loss; up to 17% in trial data

4
Week 24–48

Up to 24% total body weight loss (Phase 2 data)

Based on community reports and published research. Individual results vary significantly.

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Dosing protocols

Phase 2 trial protocol

Dose

Start 1 mg, titrate to 8–12 mg

Frequency

Once weekly (subcutaneous)

Duration

48 weeks in trials

Dosing information is sourced from published research and community protocols. This is not a recommendation. Consult a healthcare professional.

Research status|Phase 3 clinical trials - Phase 2 data published (NEJM 2023)

Overview

Retatrutide is Eli Lilly's investigational triple agonist that simultaneously activates GIP, GLP-1, and glucagon receptors. While semaglutide targets GLP-1 alone and tirzepatide targets GIP+GLP-1, retatrutide adds glucagon receptor activation. Glucagon promotes hepatic fat oxidation, increases energy expenditure, and enhances thermogenesis. Phase 2 data (published in NEJM, 2023) showed average weight loss of 24.2% at the highest dose over 48 weeks - surpassing both semaglutide and tirzepatide. Phase 3 trials are currently underway with results expected in 2025–2026.

How it works

Retatrutide combines three mechanisms: GLP-1 receptor activation (appetite suppression, insulin secretion), GIP receptor activation (fat metabolism, insulin sensitivity), and glucagon receptor activation (hepatic fat oxidation, energy expenditure, thermogenesis). The glucagon component is what distinguishes it from tirzepatide. Glucagon increases metabolic rate and promotes the liver to burn fat for energy. The challenge is balancing glucagon's hyperglycaemic effect with the glucose-lowering effects of GLP-1 and GIP - retatrutide's molecular design achieves this balance.

Side effects

Nausea and vomiting (GI effects)
moderateCommon
Diarrhoea
moderateCommon
Decreased appetite
mildCommon
Not yet approved - full safety profile still being established
moderateRare

Research history

2022

Phase 2 trial results show up to 24% weight loss - highest of any GLP-1 class drug

2023

Triple agonist mechanism (GLP-1/GIP/glucagon) generates significant interest

2024

Phase 3 trials underway by Eli Lilly

2025

Research peptide versions become available through compounders

The weight loss progression

The evolution of pharmaceutical weight loss has been dramatic: semaglutide achieved ~17% (2021), tirzepatide reached ~21% (2022), and retatrutide showed 24.2% (2023). Each generation adds receptor targets for compounding metabolic effects. If Phase 3 data confirms Phase 2 results, retatrutide would become the most effective weight loss medication ever approved. The glucagon component is particularly interesting because it increases energy expenditure - addressing one of the limitations of GLP-1-only agonists where metabolic rate can decline with weight loss.

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Core Supplies

Bacteriostatic Water 30mL

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Storage & Transport

Portable Insulin Cooler Fridge

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Further Reading

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References

  1. [1]Rosenstock J, et al. "Retatrutide, a GIP, GLP-1, and glucagon receptor agonist, for people with type 2 diabetes." The Lancet, 2023.
  2. [2]Jastreboff AM, et al. "Triple hormone receptor agonist retatrutide for obesity." New England Journal of Medicine, 2023.

Frequently asked questions

Related peptides

Tirzepatide

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The dual-action GLP-1 that outperforms Ozempic in every trial

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Semaglutide

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The GLP-1 agonist behind the weight loss revolution

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Community experiences

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Disclaimer: This guide is for educational and informational purposes only. It is not medical advice. The dosing protocols listed are sourced from published research and community reports and do not constitute a recommendation. Always consult a qualified healthcare professional before using any peptide. Check your local regulations regarding peptide purchase and use.