RESEARCH MONOGRAPH · KDC-MN-084

Retatrutide

May 9, 2026 Kodiac biolabs Research Revised May 30, 2026 2 min read

Our opinion on this compound

75/100

Triple-incretin agonist with the highest weight-loss numbers ever recorded in a phase 2 trial and serious pharmacology behind it

Retatrutide is Lilly's triple GIP/GLP-1/glucagon agonist and the phase 2 data is honestly stunning. The 12 mg dose produced 24.2% body weight reduction at 48 weeks (Jastreboff 2023, NEJM), which is the highest weight-loss percentage ever recorded in a placebo-controlled obesity trial. Phase 3 (TRIUMPH) is ongoing and the early readouts are tracking the phase 2 trajectory.

What we like is that the glucagon agonism arm is doing real work and the mechanism makes sense. GLP-1 suppresses appetite and improves glycemia, GIP modulates fat metabolism and adds to appetite suppression, glucagon increases energy expenditure through hepatic and brown adipose tissue effects. So you're hitting weight loss through three independent levers simultaneously: reduced intake (GLP-1, GIP central), improved metabolism (GIP), and increased expenditure (glucagon). The thermogenic component is the underexplored angle and partially accounts for the phase 2 numbers exceeding even tirzepatide's.

What we dont like is mostly the uncertainty profile. Retatrutide is newer than semaglutide and tirzepatide, the safety database is much smaller, and the glucagon agonism arm has the theoretical concern of insulin resistance at chronic supraphysiological glucagon receptor activation. The phase 2 data on glycemic parameters was actually reassuring (HbA1c improvements were maintained), but long-term hepatic and pancreatic effects of chronic glucagon agonism are still being characterized. The GI tolerability profile is at least as challenging as tirzepatide.

Sourcing for research-use is hard. Retatrutide is a 39-residue triple-receptor-targeted modified peptide and the synthesis is genuinely demanding. The price for HPLC+MS verified material reflects this, and cheap-end suppliers are essentially guaranteed to have purity issues that affect the receptor selectivity profile. This is not a compound to cheap out on.

For research on multi-receptor metabolic pharmacology and the frontier of incretin-based therapeutics, retatrutide is the reference compound for what the field is moving toward. The thermogenic component is the most interesting underexplored angle and genuinely promising. This is one of the most pharmacologically ambitious peptides currently in late-stage trials.

Evidence: 78
Mechanism: 88
Reliability: 82
Safety: 70
Sourcing: 55
Value: 55
Signal: 90
Staying power: 85

Plain-language summary Intrigue 91 / 100

Retatrutide is a triple agonist activating GLP-1, GIP, and glucagon receptors simultaneously. The glucagon component adds a fat-burning effect on top of the appetite suppression and glucose control of GLP-1/GIP. Phase 3 trials are ongoing for obesity. Not stocked by Kodiac. This monograph is provided for research and educational reference.

Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.

GIP/GLP-1/glucagon triple receptor agonist

An Eli Lilly investigational triple receptor agonist of GIP, GLP-1, and glucagon receptors with Phase 3 trials in obesity producing 24% weight loss at 48 weeks.

Abstract

Retatrutide (LY3437943) is an investigational triple agonist of the GIP, GLP-1, and glucagon receptors developed by Eli Lilly and currently in Phase 3 trials for obesity, type 2 diabetes, and metabolic dysfunction-associated steatohepatitis (MASH). The compound builds on the GIP/GLP-1 dual agonist tirzepatide platform by adding glucagon receptor agonism, which contributes additional weight loss through hepatic energy expenditure increases and lipolytic effects. Phase 2 obesity trial results published in 2023 showed approximately 24.2 percent weight loss at 48 weeks at the highest dose, exceeding the magnitude observed with tirzepatide. The compound is not yet FDA approved; Phase 3 program is ongoing. Pharmacokinetics: weekly subcutaneous administration; half-life supports once-weekly dosing. The triple agonist class represents the current frontier of metabolic peptide development.

Mechanism of action

Triple agonist of GIP, GLP-1, and glucagon receptors. The glucagon component adds hepatic lipolysis and energy expenditure to the GIP/GLP-1 satiety effects.

Reported research dose ranges

2 to 12 mg weekly SC in Phase 2 trials.

References

Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity: a Phase 2 trial. N Engl J Med 2023.

Read the full monograph

The full reference document covers compound identification, discovery and developmental history, mechanism of action, pharmacokinetics, reported research dose ranges, sourcing and quality verification, reconstitution and handling, stack interaction considerations, and a curated reference list. Available as a research-use-only PDF download.

KDC-MN-084

The full reference document is provided strictly for research use only. It reports research dose ranges from the published literature, not instructions for use in humans or animals.

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FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

Kodiac sells research compounds for investigative use only.

Retatrutide

Abstract

Mechanism of action

Reported research dose ranges

References

Read the full monograph

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Abstract

Mechanism of action

Reported research dose ranges

References

Read the full monograph

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