MariTide (maridebart cafraglutide)

MariTide

maridebart cafraglutide · AMG 133 · Amgen · GLP-1R agonist / GIPR antagonist

"Amgen's antibody-peptide conjugate that activates the GLP-1 receptor while blocking the GIP receptor — the opposite GIP direction to tirzepatide. A long half-life allows once-monthly dosing. Phase 2 showed up to ~20% weight loss; it is now in the Phase 3 MARITIME programme. Not approved anywhere — access is trial-only."

Type

GLP-1R agonist / GIPR antagonist · antibody-peptide conjugate

Origin

Amgen · formerly AMG 133 · MARITIME Phase 3 programme

Status

Investigational everywhere · US FDA / UK MHRA / EMA: not approved (as of 2026) · access via clinical trials only · WADA: not specifically listed

Phase 2 weight loss

up to ~20% (obesity, no T2D) · up to ~17% (with T2D) at 52 weeks

Protocol summary

Studied dose

Once-monthly SubQ (Phase 2/3); no approved label

Mechanism

GLP-1R agonist + GIPR antagonist

Status

Phase 3 · no approval anywhere

Trial (Phase 2/3)

Once-monthly subcutaneous injection, dose-escalated within trials; the exact approved regimen does not yet exist

Investigational — no label; doses studied, not licensed

Community-reported

Effectively none — MariTide is a large-molecule biologic, not a research peptide; it is not meaningfully available outside trials

Anything sold as "MariTide" as a research chemical is almost certainly counterfeit

How we read the evidence

First-in-class GLP-1R agonist / GIPR antagonist antibody-peptide conjugate · Amgen · Phase 2 showed up to ~20% weight loss at 52 weeks · now in the Phase 3 MARITIME programme · not approved in any country

Structure & preclinical

MariTide (maridebart cafraglutide, formerly AMG 133) is an antibody-peptide conjugate: a monoclonal antibody that blocks the GIP receptor (GIPR), chemically linked to two peptide GLP-1 receptor agonist molecules. That structure is unusual — most incretin drugs are peptides, whereas MariTide is essentially an engineered biologic. The antibody backbone gives it a long circulating half-life, which is what enables monthly (or potentially less frequent) dosing rather than the weekly schedule of semaglutide or tirzepatide. In an early trial, the highest dose produced roughly 14.5% weight loss at 12 weeks.

Community & clinical practice

MariTide is not a research peptide and cannot be sourced the way small peptides are. It is a complex biologic manufactured by Amgen and available only inside the MARITIME clinical-trial programme. There is no legitimate grey-market supply, and any vendor claiming to sell "MariTide" or "AMG 133" as a research chemical should be treated as selling a counterfeit — you cannot reproduce an antibody-drug conjugate in a peptide vial. Pep IQ's position here is simple: this is one to watch, not to source.

Human trial data

Phase 1 → Phase 2 → Phase 3. A first-in-human study (~110 adults with obesity) established safety and showed early weight loss. The pivotal Phase 2 trial (NCT05669599, ~592 adults) reported mean weight reductions of up to ~20% in participants with obesity without type 2 diabetes, and up to ~17% in those with obesity and type 2 diabetes, over 52 weeks — with HbA1c reductions of up to ~1.6 percentage points in the diabetes cohort. Amgen advanced MariTide into the Phase 3 MARITIME programme (registered on ClinicalTrials.gov across obesity, type 2 diabetes, obstructive sleep apnoea, elevated liver fat and cardiometabolic arms), with several trials active in 2025–2026.

Regulatory status

Investigational everywhere. As of 2026, MariTide has no approval from the FDA, MHRA, or EMA and no New Drug Application or Biologics License Application has been approved. It is an investigational new drug in active Phase 3 development — legitimate access exists only through enrolment in an Amgen trial. It is not a controlled drug, but "not controlled" is not the same as available or approved. WADA does not list maridebart cafraglutide specifically, though the GLP-1 class overall is under increasing scrutiny.

Convergence

MariTide is one of the most interesting compounds in this section — a novel mechanism (GIP antagonism paired with GLP-1 agonism, the opposite GIP direction to tirzepatide), monthly dosing, and strong Phase 2 efficacy. But it is not approved anywhere, and it is a biologic you genuinely cannot source outside a trial. Long-term and cardiovascular outcome data are still to come from MARITIME. Pep IQ flags this honestly: the science is promising and worth following closely, but the only real "protocol" today is to track the trial readouts and eventual regulatory filings — not to chase a grey-market version that, for this molecule, effectively does not exist.

Origin & Background

A different path to weight loss

While most of the obesity field pursued peptide incretins, Amgen took a different route: an antibody-peptide conjugate designed around insight from human genetics. People with reduced GIP-receptor signalling tend toward lower body weight, which motivated the idea of blocking GIPR rather than activating it — the reverse of tirzepatide's GIP-agonist approach — while still activating GLP-1.

The molecule was known in development as AMG 133 and later given the generic name maridebart cafraglutide, with the brand-style name MariTide. Because the antibody backbone stays in circulation for weeks, MariTide was built for once-monthly dosing, a meaningful departure from the weekly injections that define the current GLP-1 market.

Early trials produced encouraging weight loss, and the Phase 2 programme reported up to roughly 20% mean weight reduction over 52 weeks — numbers that put it in the same conversation as the strongest incretin therapies, with a fraction of the injection frequency. On that basis Amgen moved into the large Phase 3 MARITIME programme.

Why blocking GIP is counter-intuitive: Tirzepatide, the current benchmark dual agonist, activates the GIP receptor. MariTide blocks it. Both approaches produce substantial weight loss in trials, which tells you the biology of GIP in obesity is still not fully settled — agonism and antagonism can both help, likely through different downstream effects. That scientific tension is part of why MariTide is watched so closely.

Science & Mechanism

Two receptors, opposite directions

Mechanism of Action

GLP-1R agonism: Two GLP-1-receptor-agonist peptides on the conjugate drive appetite suppression, satiety, slowed gastric emptying and glucose-dependent insulin secretion — the same foundational mechanism as semaglutide.

GIPR antagonism: The antibody backbone blocks the GIP receptor. This is the opposite of tirzepatide's GIP agonism; the genetic rationale is that lower GIPR tone is associated with reduced body weight.

Antibody-peptide conjugate: A monoclonal anti-GIPR antibody linked to GLP-1 agonist peptides via amino-acid linkers — a single molecule combining a large biologic with peptide pharmacology.

Long half-life: The antibody component keeps the drug in circulation for weeks, enabling once-monthly (potentially less frequent) subcutaneous dosing — far less often than weekly incretins.

In the Phase 2 trial, monthly MariTide produced mean weight reductions of up to about 20% over 52 weeks in participants with obesity, and up to about 17% in those who also had type 2 diabetes, alongside meaningful HbA1c improvement in the diabetes cohort. A high proportion of participants chose to continue treatment.

The trade-off, as with all potent incretin therapies, is gastrointestinal tolerability during dose escalation — and, specific to MariTide, the long-term consequences of chronic GIPR blockade are simply not yet known. That, along with cardiovascular outcomes, is what the Phase 3 MARITIME programme is designed to establish.

Benefits & Evidence

What the data shows

⚖️

Weight loss

Phase 2 (NCT05669599, ~592 adults): mean weight reduction up to ~20% in obesity without T2D and up to ~17% with T2D over 52 weeks. Efficacy competitive with the strongest incretins — at monthly dosing.

● Moderate–strong — Phase 2 (Phase 3 pending)

📅

Once-monthly dosing

The antibody backbone gives a long half-life, supporting roughly 12 injections a year versus 52 for weekly GLP-1s — a potential adherence advantage if efficacy holds in Phase 3.

● Mechanistic / PK — pharmacokinetic basis

🩸

Glycaemic control (T2D)

In the Phase 2 diabetes cohort, HbA1c fell by up to ~1.6 percentage points over 52 weeks, with a notable proportion reaching normoglycaemia.

● Moderate — Phase 2 cohort

🧬

Novel mechanism

The first GIPR-antagonist / GLP-1R-agonist to reach late-stage trials. Whether GIP blockade ultimately beats GIP agonism is an open, closely-watched scientific question.

● Emerging — mechanism under study

Things to know

Risks & considerations

Moderate

GI side effects — nausea, vomiting, diarrhoea, constipation. Dose-related, mainly during escalation, as with all GLP-1 drugs; early trials noted these particularly at rapid titration.

Unknown

Long-term GIP-antagonism effects — chronically blocking the GIP receptor is a new intervention in humans; the long-run metabolic consequences are not yet characterised.

Moderate

Muscle mass loss — as with all potent weight-loss drugs, weight lost without resistance training and adequate protein includes lean mass.

Serious

Investigational — no approved product — there is no licensed MariTide. Any "MariTide" offered outside a trial is almost certainly counterfeit, and you cannot verify the identity of an antibody conjugate in a peptide vial.

⚠ Key Warnings

MariTide is not approved anywhere. It is an investigational Phase 3 drug — legitimate access is only through enrolment in an Amgen MARITIME trial.

It is a biologic (an antibody-peptide conjugate), not a small-molecule research peptide — it cannot be meaningfully produced or sold on the grey market. Treat any such offer as counterfeit.

Long-term safety, cardiovascular outcomes, and the consequences of chronic GIPR antagonism are not yet established.

GLP-1-class cautions apply in principle (pancreatitis risk, thyroid C-cell considerations, pregnancy); definitive labelling will only come with approval.