An investigational GIP/GLP-1/glucagon triple receptor agonist. Structurally it is GIP/GLP-1/glucagon triple agonist (acylated peptide).

How strong is the evidence for Retatrutide?

PeptideHormone grades Retatrutide at the "Investigational" evidence tier — it is under active human investigation — promising, but not yet settled. It is catalogued as an engineered analog built on an endogenous hormone, and the tier is an editorial judgment about the public literature that can change as the science does.

What is the half-life of Retatrutide?

The reported circulating half-life of Retatrutide is ~6 days.

Retatrutide

An investigational GIP/GLP-1/glucagon triple receptor agonist.

AnalogInvestigationalBased on Glucagon-like peptide-1Compare with GLP-1 Compare lineage

Three receptors from one chain. The open question on this frontier is no longer whether signals can be combined, but how many.

Identity

Class: GIP/GLP-1/glucagon triple agonist (acylated peptide)
Source: Synthetic; engineered tri-agonist
Receptor: GIP + GLP-1 + glucagon receptors

Key properties

Evidence floorClinicalREF1CLIN1

Molecular weight

≈ 4,900 Da

REF

Half-life (native)

~6 days

CLIN

Model dosing

Approximate values for the native hormone; engineered analogs are often deliberately larger and far longer-acting. Each figure carries its own provenance tier, and the floor is the weakest of them - the Standard.

Mechanism

Retatrutide engages three receptors — GIP, GLP-1, and glucagon — from a single acylated peptide. Adding glucagon-receptor agonism recruits an energy-expenditure arm alongside the incretin effects. It is in clinical trials and not approved.

One acylated peptide, three receptor arms. The GLP-1 and GIP arms are the familiar incretin chord; the glucagon arm is the third note — an energy-expenditure lever the earlier dual agonists never pulled.

In depth

Metabolic peptides started as a single note. A GLP-1 agonist activates one receptor; tirzepatide added a second, the GIP receptor, from one molecule. Retatrutide adds a third — the glucagon receptor — turning the chord into a triad. All three signals travel on one acylated peptide, engineered like its predecessors to resist the enzymes that clear the native hormones in minutes so a weekly dose can hold.

The third note is the interesting one. Glucagon on its own raises blood glucose — the opposite of what a diabetes drug wants — but it also spends energy, nudging the body's resting burn upward. The design bet is that the GLP-1 and GIP arms supply enough glucose-dependent insulin to hold blood sugar in check while the glucagon arm quietly turns up expenditure. Balance the three and you recruit weight loss from both sides of the ledger: less taken in, more spent.

So far the numbers have matched the ambition. The phase 2 readout showed the largest weight reductions yet reported for the class, without a new safety signal that stopped the program. Whether that lead survives contact with phase 3 — at scale, over longer horizons, against a field that is itself moving fast — is exactly what the TRIUMPH trials exist to answer. Retatrutide is a wager on triple agonism, not yet a settled result.

Reference notes

A 'triple agonist' — incretin co-agonism extended to a third receptor.
Glucagon-receptor agonism adds an energy-expenditure arm to the GLP-1/GIP effects.
In a phase 2 obesity trial, the highest dose produced roughly a quarter of body weight lost by 48 weeks — the steepest curve reported for an incretin-class agent at the time (Jastreboff et al., NEJM 2023).
The phase 3 TRIUMPH program is the deciding evidence; retatrutide is investigational and not approved for any use.
Beyond weight, it is being studied in fatty-liver disease (MASH), osteoarthritis of the knee, and heart failure with preserved ejection fraction.

Common questions

What is Retatrutide?: An investigational GIP/GLP-1/glucagon triple receptor agonist. Structurally it is GIP/GLP-1/glucagon triple agonist (acylated peptide).
How does Retatrutide work?: Retatrutide engages three receptors — GIP, GLP-1, and glucagon — from a single acylated peptide. Adding glucagon-receptor agonism recruits an energy-expenditure arm alongside the incretin effects. It is in clinical trials and not approved.
How strong is the evidence for Retatrutide?: PeptideHormone grades Retatrutide at the "Investigational" evidence tier — it is under active human investigation — promising, but not yet settled. It is catalogued as an engineered analog built on an endogenous hormone, and the tier is an editorial judgment about the public literature that can change as the science does.
What is the half-life of Retatrutide?: The reported circulating half-life of Retatrutide is ~6 days.

Selected literature

Curated peer-reviewed reviews, sourced from PubMed. Selected for relevance, not exhaustive — open any entry on PubMed for the full record and its primary citations.

1.Effects of once-weekly subcutaneous retatrutide on weight and metabolic markers: A systematic review and meta-analysis of randomized controlled trials · Metabolism open, 2024 · PMID 39318607
2.Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity · Diabetes care, 2024 · PMID 38843460

External references

Retatrutide in the public knowledge graph — the same entity resolved across the authoritative chemistry and protein databases.