Maridebart cafraglutide (MariTide)
Investigational once-monthly peptide-antibody conjugate combining GLP-1 receptor agonism with GIP receptor antagonism. Phase 2 produced up to ~20% weight loss at 52 weeks with no plateau; six Phase 3 trials are underway.
01 Overview
Maridebart cafraglutide (MariTide, formerly AMG 133) is Amgen's obesity candidate: a monoclonal antibody against the GIP receptor conjugated to two GLP-1 receptor agonist peptides. Its ~21-day half-life allows once-monthly — and potentially once-quarterly — subcutaneous dosing, in contrast to the weekly injections of semaglutide and tirzepatide. It is investigational and not approved anywhere.
Its mechanism is a live scientific debate. Tirzepatide, the current market leader, is a GIP receptor agonist, whereas MariTide antagonises the same receptor — yet both drive substantial weight loss. In the Phase 2 trial the weight-loss curve had not plateaued at one year, which Amgen has emphasised as a differentiator.
02 Mechanism
Agonises the GLP-1 receptor to suppress appetite and slow gastric emptying while blocking the GIP receptor. The antibody backbone gives a long half-life enabling monthly or quarterly dosing.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Escalation start | 70 mg | SubQ | Phase 2 starting dose for titration arms, escalated to 420 mg |
| Monthly | 140–420 mg | SubQ | Phase 2 tested 140, 280 and 420 mg every 4 weeks |
| Extended interval | 420 mg | SubQ | Phase 2 also tested 420 mg every 8 weeks |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Weight lossPhase 2, obesity without diabetes at 52 weeks (efficacy estimand); 12.3-16.2% on the treatment-policy estimand vs ~2.5% placebo, without plateau. | up to ~20% body weight | Clinical | |
| Weight loss with type 2 diabetesPhase 2, obesity with type 2 diabetes at 52 weeks vs 1.4% placebo. | up to ~17% body weight | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Nausea and vomitingDominant adverse effects, most frequent early and after dose steps; earlier fixed-dose regimens produced high vomiting rates. | Moderate | Very common | Clinical | |
| Injection-site reactionsLocal reactions reported with the large-volume monthly subcutaneous injection. | Mild | Common | Clinical |