Maridebart cafraglutide (AMG 133, branded MariTide) is Amgen's investigational obesity therapy combining a monoclonal antibody targeting GIP receptor antagonism with two conjugated GLP-1 receptor agonist peptides. The design enables once-monthly subcutaneous administration, a substantially lower administration burden than weekly GLP-1 incretins.
Mechanism: GIP Antagonism plus GLP-1 Agonism
MariTide is mechanistically unusual: it agonises the GLP-1 receptor while antagonising the GIP receptor. This contrasts with Tirzepatide and VK2735, which agonise both. The rationale derives from preclinical and genetic evidence suggesting GIP receptor antagonism may itself contribute to weight reduction, possibly via altered adipose signalling [1].
Phase 2 Data
52-week Phase 2 results reported mean weight reduction of approximately 20% at the highest dose, with continued body-weight reduction observed through the end of treatment. The pharmacokinetic profile supports monthly or even less frequent administration, with sustained drug exposure between doses [2].
Format: Peptide-Antibody Conjugate
MariTide is not a conventional peptide. It is a bispecific peptide-antibody conjugate, structurally closer to therapeutic antibodies than to GLP-1 peptides. This format is not amenable to standard solid-phase peptide synthesis and is not available as a research-grade compound from peptide suppliers.
Research Pathways
Laboratories interested in GIP antagonism alongside GLP-1 agonism currently model the combination using Semaglutide as the GLP-1 reference and dedicated GIP receptor antagonist tool compounds available through specialist chemistry suppliers. Tirzepatide serves as the dual agonist comparator.
References
- [1] Killion EA, et al. "Anti-obesity effects of GIPR antagonists." Sci Transl Med. 2018.
- [2] Amgen MariTide Phase 2 readout, 2025-2026 disclosures.