MariTide (AMG 133): Mechanism, Research & UK Safety Profile
Also known as: AMG 133, maridebart cafraglutide
Investigational peptide-antibody conjugate developed by Amgen. Combines GIP receptor antagonism (delivered by the antibody backbone) with GLP-1 receptor agonism (peptide payload). Designed for monthly subcutaneous administration. Phase 2 obesity data published. Not MHRA-licensed.
Overview
MariTide (AMG 133, maridebart cafraglutide) is an investigational peptide-antibody conjugate combining GIP receptor antagonism (delivered by the antibody backbone) with GLP-1 receptor agonism (peptide payload). The combination is mechanistically distinct from the dual GLP-1/GIP agonist class (tirzepatide), in that GIP receptor activity is antagonised rather than agonised. The molecule's antibody-conjugate format enables monthly subcutaneous dosing. Phase 2 obesity data has been published; phase 3 development is in active progression. MariTide is investigational.
Discovery & Research History
AMG 133 emerged from Amgen's peptide-antibody conjugate programme. Phase 1 pharmacokinetic and pharmacodynamic data and phase 2 obesity data (NEJM 2024) established a substantial mean body-weight reduction signal in the studied cohort with monthly subcutaneous dosing.
Mechanism of Action
The antibody scaffold delivers GIPR antagonism while the conjugated peptide delivers GLP-1 receptor agonism. The pharmacological rationale (GIPR antagonism + GLP-1R agonism) is supported by preclinical observations that some GIPR activity may attenuate weight-loss effects, though the mechanistic understanding of GIP in this context remains under active research.
Researched Effects
- Substantial mean body-weight reduction reported in phase 2 obesity data.
- Monthly subcutaneous dosing schedule (lower frequency than weekly incretin agents).
Theoretical Research Protocols
- Dosage range
- Trial-arm doses are research records.
- Frequency
- Monthly subcutaneous administration in trial protocols.
- Duration
- 52 weeks in pivotal phase 2 reports; phase 3 designs extend beyond.
- Administration routes
- Subcutaneous (clinical trial setting)
Safety Profile
Common side effects (research)
- Gastrointestinal events (notably vomiting reported in phase 2).
- Injection-site reactions.
Rare risks
- Long-term safety of GIPR antagonism in combination with GLP-1R agonism remains to be characterised through phase 3.
- Immunogenicity considerations apply to antibody-based therapeutics.
Contraindications
- Investigational compound; eligibility per current trial protocol.
UK Regulatory Status
United Kingdom (MHRA): Investigational. Not MHRA-licensed.
European Union (EMA): Investigational.
Notes: MariTide is the most clinically advanced peptide-antibody conjugate in the metabolic peptide landscape at the time of review.
Related research resources
Key Research Studies
Veniant MM et al. MariTide (AMG 133) phase 1 / phase 2 obesity data — NEJM 2024
Phase 1 pharmacokinetic and pharmacodynamic data and phase 2 obesity data reporting substantial mean percent body-weight reduction with monthly subcutaneous MariTide versus placebo.
Read sourceAmgen MariTide phase 3 programme
Phase 3 development in obesity and adjacent indications; refer to ClinicalTrials.gov for current programme status.
Frequently Asked Questions
What is MariTide?
An investigational peptide-antibody conjugate developed by Amgen. The antibody backbone delivers GIP receptor antagonism while the conjugated peptide delivers GLP-1 receptor agonism. Designed for monthly subcutaneous administration.
How does MariTide differ from tirzepatide?
Tirzepatide is a GLP-1 / GIP dual agonist — it activates both receptors. MariTide antagonises the GIP receptor while agonising the GLP-1 receptor. The two molecules approach the GIP receptor from opposite directions, and head-to-head trial data would be required to characterise the comparative clinical effect.
Is MariTide licensed?
No. MariTide is investigational worldwide at the time of review.
Related trials
No published trials yet linked to this page. Source verification required.