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Metabolic

MariTide (maridebart cafraglutide)

Also known as Maridebart cafraglutide · AMG 133 · AMG133 · MariTide · Anti-GIPR antibody / GLP-1 peptide conjugate · GIPR antagonist / GLP-1R agonist antibody-peptide conjugate

InvestigationalAHuman trial evidenceWhat this means

MariTide (maridebart cafraglutide, AMG 133) is not a peptide but an antibody-peptide conjugate: synthetic GLP-1 receptor agonist peptides chemically attached to an anti-GIP-receptor monoclonal antibody, investigational for obesity, with a 592-participant phase 2 trial reporting body-weight change of -12.3% to -16.2% at 52 weeks and phase 3 trials under way.

US status
Investigational
Evidence
Grade A
Half-life
Not reported numerically in the sources reviewed. The conjugate design is described as giving markedly prolonged systemic exposure of the structurally intact GLP-1 peptide, and the phase 2 trial administered it once every 4 or 8 weeks 1,6.
Class
Antibody-peptide conjugate: anti-GIP-receptor monoclonal IgG antibody conjugated to synthetic GLP-1 receptor agonist peptides (not a peptide drug)
Studied in: Appetite & body weight
More
Log a sample
Dosing referenceCycle-length evidence
Unbranded reference vial illustrating MariTide (maridebart cafraglutide); not an actual product
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Key takeaways

  • MariTide is an antibody-peptide conjugate, not a peptide: synthetic GLP-1 receptor agonist peptides attached to an anti-GIP-receptor monoclonal antibody, so it has no single peptide sequence 4,6.
  • It combines two opposite-direction incretin actions in one molecule: GLP-1 receptor agonism and GIP receptor antagonism 1,5.
  • In the published phase 2 trial, mean body-weight change at week 52 was -12.3% to -16.2% versus -2.5% with placebo in the obesity cohort, and -8.4% to -12.3% versus -1.7% in the obesity plus type 2 diabetes cohort 1.
  • Gastrointestinal adverse events were common and were less frequent with dose escalation and a lower starting amount; the authors reported no unexpected safety signals in phase 2 1.
  • It is not approved anywhere in the sources reviewed; a large phase 3 cardiovascular outcomes trial is recruiting 8,9.

Development stage

Where MariTide (maridebart cafraglutide) sits between laboratory work and regulatory approval.

  1. Preclinical
  2. Phase 1
  3. Phase 2
  4. Phase 3 (current)
  5. Approved

Stage comes from the regulatory record and ClinicalTrials.gov studies naming the compound (for compounds approved nowhere, only completed trials or trials with posted results count) (checked 2026-10-24). A registered trial is not a result.

Mechanism of action

Maridebart cafraglutide is built from an IgG monoclonal antibody directed against the GIP receptor, to which synthetic GLP-1 analogue peptides are chemically conjugated 4,6. The design decouples peptide synthesis from antibody expression, which allows non-natural amino acids and other chemical modifications in the peptide portion, while the antibody provides the long circulating exposure that a free peptide cannot 4.

Dual, opposite-direction incretin action

  • GLP-1 receptor agonism: the conjugated peptides act as GLP-1 receptor agonists, the mechanism shared with established incretin drugs 1.
  • GIP receptor antagonism: the antibody blocks rather than activates the GIP receptor, which is the opposite of the GIP-agonist component in dual GIP/GLP-1 agonists; reviews note that both GIP agonism and GIP antagonism have produced body-weight reduction in trials and that the reasons are still debated 5,12.

Exposure

The discovery paper reports that conjugation gave markedly prolonged systemic exposure of the structurally intact GLP-1 peptide, with once-weekly administration producing sustained effects in diet-induced obese mice and obese monkeys, and a profile the authors said may support monthly administration in people 6. The phase 2 trial used 4-weekly and 8-weekly administration accordingly 1.

Research overview

Human research

The published human evidence is one phase 2 trial plus phase 1 studies. The phase 2 double-blind, randomised, placebo-controlled dose-ranging trial (NCT05669599) enrolled 592 participants across 11 groups in two cohorts. In the obesity cohort (465 participants, 63% female, mean age 47.9 years, mean BMI 37.9), mean percent body-weight change from baseline to week 52 on the treatment policy estimand ranged from -12.3% (95% CI -15.0 to -9.7) to -16.2% (95% CI -18.9 to -13.5) versus -2.5% (95% CI -4.2 to -0.7) with placebo. In the obesity plus type 2 diabetes cohort (127 participants, mean BMI 36.5), the range was -8.4% to -12.3% versus -1.7% with placebo, and HbA1c changed by -1.2 to -1.6 percentage points versus +0.1 with placebo 1. A first-in-human single and multiple ascending dose study in 110 participants with obesity (NCT04478708) is listed as completed 7. The phase 3 programme includes a cardiovascular outcomes trial with an estimated 12,800 participants in atherosclerotic cardiovascular disease plus overweight or obesity (NCT07037433, recruiting), a type 2 diabetes trial (NCT06858878) and a heart failure trial in preserved or mildly reduced ejection fraction with obesity (NCT07037459) 9,10,11. Published correspondence in the New England Journal of Medicine debates the phase 2 findings 2,3.

Animal research

In diet-induced obese mice and obese monkeys, once-weekly administration of anti-GIPR antibody/GLP-1 peptide conjugates produced sustained body-weight reduction and improvements in metabolic parameters; this series of experiments led to the selection of AMG 133 6.

In-vitro research

The conjugates were characterised for GIP receptor antagonism and GLP-1 receptor agonism during optimisation, with conjugation reported to preserve the structurally intact GLP-1 peptide while prolonging its exposure 6.

Key studies

  1. Jastreboff et al. phase 2 trial, N Engl J Med (NCT05669599) (2025)
    Phase 2, double-blind, randomised, placebo-controlled dose-ranging trial with 11 groups in two cohorts; primary endpoint percent change in body weight at week 52; funded by Amgen
    Model: Humans (592 participants: 465 with obesity, 127 with obesity and type 2 diabetes)

    Mean body-weight change at week 52 was -12.3% to -16.2% versus -2.5% with placebo (obesity cohort) and -8.4% to -12.3% versus -1.7% (obesity-diabetes cohort); HbA1c fell 1.2 to 1.6 percentage points versus +0.1 with placebo; gastrointestinal adverse events were common but less frequent with dose escalation and a lower starting amount.

  2. Wu et al., J Med Chem (2026)
    Design and optimisation of antibody-peptide conjugates with receptor assays and once-weekly dosing experiments
    Model: Cells and animals (diet-induced obese mice, obese monkeys)

    Conjugation of synthetic GLP-1 peptides to anti-GIPR IgG antibodies gave markedly prolonged exposure of the intact peptide and sustained body-weight reduction in both species, culminating in the selection of AMG 133.

  3. Yie et al., Antib Ther (review) (2026)
    Narrative review of antibody-peptide conjugate design using AMG 133 as the central case
    Model: Not applicable

    Describes the rationale for conjugates over fusion proteins: decoupled synthesis allowing non-proteinogenic residues and cyclic structures, with antibody-like half-life; authors are employees of a company developing conjugates.

  4. NCT04478708 (Amgen) (2026)
    Phase 1 single and multiple ascending dose study assessing safety and tolerability
    Model: Humans (110 participants with obesity)

    Listed as completed in the registry; results are summarised in the development literature rather than in the registry record reviewed.

  5. NCT07037433 (Amgen) (2026)
    Phase 3 cardiovascular outcomes trial, estimated enrolment 12,800
    Model: Humans (adults with atherosclerotic cardiovascular disease and overweight or obesity)

    Recruiting as of 24 October 2026; no results posted.

Doses used in published trials

What investigators administered in the cited studies, recorded as a fact about those studies. Not a protocol and not a recommendation.

Full dosing reference, study durations and vial arithmetic →
  • In the phase 2 dose-ranging trial (NCT05669599), participants in the obesity cohort were randomly assigned to subcutaneous maridebart cafraglutide 140, 280 or 420 mg every 4 weeks without dose escalation; 420 mg every 8 weeks without dose escalation; 420 mg every 4 weeks with 4-week dose escalation; 420 mg every 4 weeks with 12-week dose escalation; or placebo, for 52 weeks 1.
  • In the same trial, participants in the obesity plus type 2 diabetes cohort were randomly assigned to 140, 280 or 420 mg every 4 weeks, all without dose escalation, or placebo 1.
  • The first-in-human study (NCT04478708) used single and multiple ascending amounts in participants with obesity to assess safety and tolerability; amounts are not stated in the registry record reviewed 7.

Published adverse-event data

Reported in the cited trials or product labels. Frequencies apply to the stated population and do not transfer to other settings.

  • Gastrointestinal adverse events
    Described as common with maridebart cafraglutide, and less frequent in groups using dose escalation and a lower starting amount; exact rates not given in the abstract reviewed
    Phase 2 trial, 592 participants, 52 weeks 1 · Not graded in the abstract reviewed
  • Unexpected safety signals
    None reported
    Phase 2 trial, 52 weeks 1 · Investigators' summary statement

Emerging safety signals

  • Tolerability in phase 2 depended on how administration was started: gastrointestinal events were less frequent with dose escalation and a lower starting amount, and two of the eleven groups were included specifically to test 4-week and 12-week escalation schemes 1. 1 (2025)
  • As an antibody-based molecule with prolonged exposure, adverse effects cannot be stopped quickly by withdrawal in the way a short-acting peptide allows; the sources reviewed report no immunogenicity data for the conjugate 4,6. 4 (2026)

What is not known: No phase 3 efficacy or safety results were available in the sources reviewed; the cardiovascular outcomes, type 2 diabetes and heart failure trials are ongoing without posted results 9,10,11. Published half-life values, immunogenicity data and long-term safety for the conjugate were not located 4,6. Whether GIP receptor antagonism contributes to the observed body-weight change, and how it compares with GIP agonism as used in dual agonists, remains debated in the reviews reviewed 5,12. No head-to-head trial against an approved incretin drug was located, so the phase 2 percentages cannot be read as a comparison 1.

Background viewing

We haven't found a clinician video focused on MariTide (maridebart cafraglutide) yet. Meanwhile, this widely watched talk covers the science of aging in general. It does not discuss MariTide (maridebart cafraglutide).

David Sinclair, PhD (Harvard Medical School) on the biology of aging
The Diary Of A CEO · 6.9M views · 2026

These creators are not affiliated with Amiravo and do not endorse Amiravo or any product linked on this site. Nothing here is medical advice. Video views counted on YouTube as of Oct 24, 2026.

Regulatory status

Status
Investigational. No Drugs@FDA application record was returned for maridebart cafraglutide on 24 October 2026 8. A phase 2 dose-ranging trial of 592 participants has been published 1, and Amgen has registered a phase 3 programme including a cardiovascular outcomes trial with an estimated 12,800 participants (NCT07037433, recruiting), a type 2 diabetes trial (NCT06858878) and a heart failure trial (NCT07037459) 9,10,11.
United States (FDA)
Not approved. An openFDA Drugs@FDA query for maridebart cafraglutide returned no application record on 24 October 2026 8. Phase 3 trials are registered and recruiting 9,10,11.
Sport (WADA)
Not named individually in the sources reviewed; S0 covers substances without governmental approval for human therapeutic use, prohibited at all times 13.

Status varies by country and changes over time. How we describe regulatory status.

Quality and testing notes

This molecule is a biologic manufactured by antibody expression plus peptide synthesis and conjugation, so the quality questions are different from those for a synthetic peptide: identity and integrity of the antibody, the peptide-to-antibody ratio and conjugation site, aggregate and fragment content, host-cell protein and residual DNA, and endotoxin [4, 6]. Material offered as a research peptide version of MariTide cannot be the same molecule, since a conjugate of this kind cannot be produced by peptide synthesis alone; no sequence, formula or PubChem identifier is listed in this entry for that reason [4].

How purity testing works · Reading a certificate of analysis

Check a MariTide (maridebart cafraglutide) certificate of analysis

Storage and handling

Antibody-based biologics are generally handled cold, protected from freezing, agitation and light, and are sensitive to aggregation; follow the sponsor's or supplier's documentation. No temperatures or preparation steps are given here.

Frequently asked questions

Is MariTide a peptide?
No. Maridebart cafraglutide is an antibody-peptide conjugate: synthetic GLP-1 receptor agonist peptides chemically attached to a monoclonal antibody against the GIP receptor, so it has no single peptide sequence 4,6.
How does it differ from tirzepatide-style dual agonists?
It antagonises the GIP receptor rather than activating it, while also agonising the GLP-1 receptor. Reviews note that both GIP agonism and antagonism have been associated with body-weight reduction and that the mechanism behind this is still debated 5,12.
What did the phase 2 trial report?
In 592 participants, mean body-weight change at week 52 was -12.3% to -16.2% versus -2.5% with placebo in the obesity cohort, and -8.4% to -12.3% versus -1.7% in the obesity plus type 2 diabetes cohort, where HbA1c also fell by 1.2 to 1.6 percentage points versus +0.1 1.
How often was it given in trials?
In the phase 2 trial it was given subcutaneously every 4 weeks, with one group every 8 weeks; the molecule was designed for prolonged exposure through its antibody component 1,6.
What were the main adverse events?
Gastrointestinal adverse events were common, and were less frequent in the groups that used dose escalation and a lower starting amount; the investigators reported no unexpected safety signals in phase 2 1.
Is it approved?
No. An openFDA Drugs@FDA query returned no application record on 24 October 2026, and phase 3 trials including a 12,800-participant cardiovascular outcomes trial are ongoing 8,9.
Can research suppliers sell MariTide?
A conjugate of a monoclonal antibody and synthetic peptides cannot be produced by peptide synthesis, so material sold under this name as a research peptide is not the same molecule 4.
Is it banned in sport?
It is not named individually in the sources reviewed; S0 covers substances with no current governmental approval for human therapeutic use, prohibited at all times, so athletes should consult their anti-doping organisation 13.

Latest indexed research

Search all studies on MariTide (maridebart cafraglutide) (PubMed, Europe PMC, ClinicalTrials.gov)

Listed by publication type from the index record. Inclusion is not an endorsement; open the source to read the findings.

Revision history

Meaningful changes to this entry, with dates and sources. Last reviewed Oct 24, 2026. Typo and layout fixes are not listed.

  • New section· entryOct 24, 2026

    New research reference added: MariTide (maridebart cafraglutide).

References

  1. Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity - A Phase 2 Trial N Engl J Med. 2025
  2. Once-Monthly Maridebart Cafraglutide in Obesity - A Phase 2 Trial (correspondence) N Engl J Med. 2025
  3. Once-Monthly Maridebart Cafraglutide in Obesity - A Phase 2 Trial. Reply N Engl J Med. 2025
  4. Design and therapeutic rationale of antibody-peptide conjugates: insights from maridebart cafraglutide (AMG133) and emerging applications Antib Ther. 2026
  5. Bidirectional pharmacology of GIP receptor targeting in obesity: Historical foundations, mechanistic divergence, and translational boundaries Peptides. 2026
  6. Discovery of AMG 133, a Glucose-Dependent Insulinotropic Polypeptide Receptor Antagonist and Glucagon-Like Peptide 1 Receptor Agonist Antibody-Drug Conjugate for the Treatment of Obesity J Med Chem. 2026
  7. Single and Multiple Ascending Dose Study of AMG 133 in Participants With Obesity (NCT04478708) ClinicalTrials.gov. 2026
  8. Drugs@FDA application data queried through openFDA for maridebart cafraglutide (no matching application record returned on 24 October 2026) openFDA / Drugs@FDA. 2026
  9. Evaluating the Impact of Maridebart Cafraglutide on Cardiovascular Outcomes in Participants With Atherosclerotic Cardiovascular Disease and Overweight or Obesity (NCT07037433) ClinicalTrials.gov. 2026
  10. Efficacy and Safety of Maridebart Cafraglutide in Adult Participants With Type 2 Diabetes Mellitus and Overweight or Obesity (NCT06858878) ClinicalTrials.gov. 2026
  11. Maridebart Cafraglutide in Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Obesity (NCT07037459) ClinicalTrials.gov. 2026
  12. One receptor, two opposite approaches: efficacy and tolerability of GIPR agonism and antagonism in obesity pharmacotherapy Appetite. 2026
  13. International Standard: Prohibited List 2026 World Anti-Doping Agency. 2026

Last reviewed October 24, 2026 by the Amiravo editorial team.

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For research use only. Not for human or veterinary use. Not a drug, food, or dietary supplement. This page is educational and is not medical advice.

Unbranded reference vial illustrating MariTide (maridebart cafraglutide); not an actual product

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Specifications

Type
Single compound

Chemical identifiers are shown only when verified against PubChem.

Research stats

How much has been published, not how good it is.

PubMed records
27
Indexed as human research
15
Animal-only research
2
Randomized controlled trials
2
Registered trials
30
Trials with posted results
2
2006: 02007: 02008: 02009: 02010: 02011: 02012: 02013: 02014: 02015: 02016: 02017: 02018: 02019: 02020: 02021: 12022: 12023: 22024: 62025: 82026: 1120062026
PubMed records per year (current year is partial).

Counts from title/abstract searches of PubMed, ClinicalTrials.gov, openFDA and NIH RePORTER, checked 2026-10-24. Names shared with other substances can inflate counts. FAERS reports are spontaneous and do not establish cause. Funding shows interest, not evidence. Method

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