What is Maridebart cafraglutide (MariTide)?

GLP-1 agonism paired with GIP receptor antagonism — the opposite GIP direction to tirzepatide. Structurally it is GLP-1 agonist–GIP-antagonist peptide–antibody conjugate.

How strong is the evidence for MariTide?

PeptideHormone grades MariTide 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 MariTide?

The reported circulating half-life of MariTide is ~21 days (monthly dosing).

Maridebart cafraglutideMariTide

GLP-1 agonism paired with GIP receptor antagonism — the opposite GIP direction to tirzepatide.

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

Turning the GIP receptor off also works, which makes this the most instructive puzzle on the metabolic frontier.

Identity

Class: GLP-1 agonist–GIP-antagonist peptide–antibody conjugate
Source: Synthetic; anti-GIP-receptor antibody conjugated to GLP-1 peptides
Receptor: GLP-1 receptor (agonist) + GIP receptor (antagonist)

Key properties

Evidence floorClinicalREF1CLIN1

Molecular weight

≈ 150,000 Da

REF

Half-life (native)

~21 days (monthly dosing)

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

Maridebart cafraglutide pairs GLP-1 receptor agonism with GIP receptor antagonism on a single peptide–antibody conjugate — an anti-GIP-receptor antibody carrying GLP-1 peptides. It blocks the very GIP receptor that tirzepatide activates, yet also drives weight loss, and its antibody scaffold gives a long half-life that enables once-monthly dosing. It is investigational.

The same two arms as tirzepatide, one of them inverted. GLP-1R is switched on; the GIP arm reaches its receptor only to switch it off. That both directions on the same receptor reduce weight is the paradox the design leans into.

In depth

Read the incretin story left to right and it looks like a march toward more: semaglutide plays one receptor, tirzepatide two, retatrutide three. Maridebart cafraglutide breaks the pattern by turning one of the notes the wrong way. It agonizes the GLP-1 receptor like the rest of the class, but at the GIP receptor it does the opposite of what tirzepatide does — it blocks it. Two drugs, the same receptor, opposite directions, and both take weight off. That contradiction is the single most instructive puzzle on the metabolic frontier, and this molecule is built around it.

The design is also a departure in form. Where the others are acylated peptides tethered to albumin, maridebart is a peptide–antibody conjugate: GLP-1 peptides carried on an anti-GIP-receptor antibody. The antibody is not just a passenger — it is the reason the GIP arm blocks rather than activates, and it is the reason the whole molecule lingers. An antibody scaffold is recycled by the same salvage machinery that keeps native antibodies in circulation for weeks, so the dosing interval stretches from weekly toward once a month.

How the paradox resolves is still open. Sustained GIP agonism may desensitize the receptor until it behaves as if blocked, making agonism and antagonism converge; or the two may act in different tissues; or the field simply does not yet understand what the GIP receptor contributes to weight. Maridebart is the clean experiment — a deliberate, durable GIP blockade set beside GLP-1 agonism — and its trials are where that question gets answered rather than argued.

Reference notes

Turns the GIP receptor off while turning GLP-1 on — the opposite GIP direction to tirzepatide, and both approaches reduce weight.
Built as a peptide–antibody conjugate, whose long half-life supports once-monthly dosing.
Investigational — phase 2 reported, larger trials ongoing.

Common questions

What is Maridebart cafraglutide (MariTide)?: GLP-1 agonism paired with GIP receptor antagonism — the opposite GIP direction to tirzepatide. Structurally it is GLP-1 agonist–GIP-antagonist peptide–antibody conjugate.
How does MariTide work?: Maridebart cafraglutide pairs GLP-1 receptor agonism with GIP receptor antagonism on a single peptide–antibody conjugate — an anti-GIP-receptor antibody carrying GLP-1 peptides. It blocks the very GIP receptor that tirzepatide activates, yet also drives weight loss, and its antibody scaffold gives a long half-life that enables once-monthly dosing. It is investigational.
How strong is the evidence for MariTide?: PeptideHormone grades MariTide 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 MariTide?: The reported circulating half-life of MariTide is ~21 days (monthly dosing).

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.Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity - A Phase 2 Trial · The New England journal of medicine, 2025 · PMID 40549887
2.A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings · Nature metabolism, 2024 · PMID 38316982

External references

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