Maridebart Cafraglutide (MariTide)
Also known as: MariTide, AMG 133, Maridebart cafraglutide
MariTide is a once-monthly peptide-antibody conjugate that activates the GLP-1 receptor while blocking the GIP receptor — the opposite GIP strategy from tirzepatide, and the most mechanistically unusual drug in late-stage obesity development.
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Mechanism of Action
Maridebart cafraglutide is a peptide-antibody conjugate: GLP-1 receptor agonist peptides conjugated to a monoclonal antibody that antagonizes the GIP receptor. The antibody scaffold confers a very long half-life, enabling monthly or less frequent dosing. Mechanistically it is notable for GIP receptor blockade — the opposite of tirzepatide's GIP agonism — a strategy supported by human genetics work with deCODE Genetics that identified GIP receptor loss-of-function variants as associated with lower body weight. That two opposing GIP strategies both produce weight loss remains an active question in the field.
- Half-life
- Antibody-conjugate design supports once-monthly or less frequent subcutaneous dosing
- Administration Routes
- subcutaneous
- Research Status
- Clinical
Reported Benefits
- Up to approximately 20% body weight loss at 52 weeks in phase 2 (vs 2.6% placebo)
- Once-monthly dosing — a substantial adherence advantage over weekly injectables
- No weight-loss plateau observed through the phase 2 period
- Phase 3 MARITIME program spans six global trials
- Mechanistically distinct from every approved incretin drug
Potential Side Effects
- Gastrointestinal adverse events, notably nausea and vomiting
- Tolerability with monthly bolus dosing is a key open question
- Long-term safety not established
- Full phase 3 adverse-event profile not yet reported
Common Dosing
No established human dosing outside clinical trials. Phase 2 evaluated once-monthly subcutaneous dosing over 52 weeks. MariTide is investigational and not approved for human use. Not medical or dosing advice.
The dosing information above is aggregated from research literature and anecdotal community reports for educational purposes only. It is not a recommendation, prescription, or medical advice. Peptides are sold as research chemicals only and are not intended for human use.
Contraindications
- Not approved for human use in any jurisdiction
- Pregnancy and breastfeeding
- Personal or family history of medullary thyroid carcinoma or MEN2 (class-wide precaution for GLP-1 receptor agonists)
No documented stacking partners for Maridebart Cafraglutide (MariTide) yet.
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Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity - A Phase 2 Trial
2025
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A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings
2024
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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
2026
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Design and therapeutic rationale of antibody-peptide conjugates: insights from maridebart cafraglutide (AMG133) and emerging applications
2026