COMPOUND

Compounds / GLP-1 agonists

MariTide

Maridebart cafraglutide (AMG 133)

GLP-1 agonists SubQ Investigational

Investigational once-monthly (or less frequent) peptide-antibody conjugate that combines GLP-1 receptor agonism with GIP receptor ANTAGONISM: mechanistically opposite to tirzepatide on the GIP arm. Phase 2 (NEJM 2025): up to 16-20% weight loss at 52 weeks with monthly dosing. Phase 3 MARITIME program ongoing 2025-2026. Unique selling proposition: monthly dosing + reported weight maintenance after washout (reduced rebound vs other GLP-1 RAs).

At a glance

Half-life
~21 days ~21 days estimated from monthly dosing schedule and steady-state achieved by week 8. Slow absorption from SC site (mAb component); Tmax days to weeks. PK details still emerging.
Routes
SubQ
Evidence base
1 study 1 human

Mechanism

Bispecific peptide-antibody conjugate. Antibody backbone (anti-GIPR monoclonal) antagonizes the GIP receptor. GLP-1 RA peptide conjugated to the antibody agonizes the GLP-1 receptor. GIP antagonism rationale: GIP normally promotes adipose lipid storage; antagonism may suppress adipogenesis. Amgen's hypothesis (initially controversial since tirzepatide AGONIZES GIP and works very well) is that chronic GIP signaling in obesity is dysregulated and antagonism corrects this. Phase 2 supports the mechanism: -12.3% to -16.2% body weight loss across dose cohorts with monthly dosing. Antibody backbone provides the long half-life (weeks) enabling monthly SC injections.

Dosing

Any amounts shown here are reported from published studies only. 1 of 1 catalogued study involved human subjects. COMPOUND does not publish its own dosing guidance.

Published evidence

  1. Human RCT 2025

    Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity: A Phase 2 Trial

    Jastreboff AM, Garcia-Salas R, Carrera Boada CA, et al. NEJM

    Phase 2, n=465 obesity (and separate T2D cohort). 52-week weight change: -12.3% to -16.2% across MariTide arms vs -2.5% placebo. T2D cohort: ~17% weight loss + HbA1c reduction up to 2.2%. GI AEs less frequent with dose escalation + lower starter dose.

    PMID 40549887

Reported side effects

Nausea
Very common Moderate · Phase 2: GI AEs common (peak post-injection day 1-7). Lower with starter dose + escalation.
Vomiting
Common Moderate · Phase 2: ~20-30% across higher doses. Concentrated in first 1-2 weeks post-injection.
Decreased appetite
Very common Mild · Wanted effect.
Injection site reactions
Common Mild · Larger volume injection due to mAb component → more site reactivity expected.
Diarrhea
Common Mild · Class effect.
Hair loss
Occasional Mild · Reported in phase 2, similar magnitude to other rapid-weight-loss therapies.
Constipation
Common Mild · Class effect.
Heart rate increase
Occasional Mild · Modest; lower than retatrutide due to lack of GCGR activity.
Hypoglycemia
Rare Moderate · T2D + SU/insulin: increased risk. Non-DM: minimal.
Pancreatitis
Rare Serious · Class warning.

Interactions

  • Insulin or sulfonylurea Synergy

    Hypoglycemia risk with insulin or SU (GLP-1 component).

  • Oral medications (general) Absorption interference

    GLP-1 mediated gastric emptying delay may affect oral drug absorption.

  • Tirzepatide Contraindicated

    Tirzepatide AGONIZES GIPR; MariTide ANTAGONIZES GIPR. Pharmacologically opposite: would null each other on the GIP arm. Concurrent use is mechanistically contradictory.

  • Semaglutide (SC) Redundant

    Overlapping GLP-1 agonism. Concurrent GLP-1 RA use not recommended.

Reconstitution and storage

N/A pre-approval. Larger injection volume expected (mAb conjugate).

N/A pre-approval. mAb products typically require strict cold chain.

Open the reconstitution calculator for MariTide