MariTide
InvestigationalA bispecific peptide-antibody conjugate combining GLP-1 receptor agonism with GIP receptor antagonism. Unique mechanism opposite to tirzepatide. The published Phase 2 trial (NCT05669599) showed up to ~16% weight loss at 52 weeks with once-monthly dosing. MARITIME Phase 3 program ongoing.
AMG 133 · maridebart cafraglutide
12 human studies
- Preclinical
- 14%
- Clinical
- 86%
Based on 14 cited sources
clinically demonstrated · moderate confidence
Demonstrated effect magnitude — not a recommendation or safety claim.
Research Depth 73: one published adequately-powered double-blind placebo-controlled Phase 2 RCT (Jastreboff NEJM 40549887, n=592, NCT05669599) at low RoB on weight (1A 28, 1B 16); total human N ~600-700 incl. Phase 1 (1C 9); direct obesity population/SC route/body-weight outcome (1D 13); substantial DIO-mouse + obese-monkey preclinical program (AMG 133 discovery 41941715, 1E 7). No second RCT, SR or meta-analysis yet (Phase 3 MARITIME ongoing), capping 1A. Mechanism 85: GLP-1R/GIPR targets with binding + functional + genetic/antagonist confirmation (GIPR variant work 38871982; gut GIPR signaling 39723966) (2A 38); incretin pathway largely mapped though the dual GIP-agonism/antagonism paradox is unresolved (2B 20); dose-response across Phase 2 doses + in-vivo models (2C 17); confirmed in mammalian in vivo incl. humans (2D 10). Plausibility 80: mechanism -> surrogate (weight, HbA1c) established, surrogate -> hard CV outcome still inferred (3A 28); coherent with incretin biology with the GIP paradox as residual tension (3B 21); multiple same-class agents (semaglutide, tirzepatide) reliably produce the effect (3C 18); tightly scoped obesity/T2D claim (3D 13). Global Coverage 55: pivotal RCT single-sponsor (Amgen) so clinical replication pending, but mechanism reproduced by independent academic groups across US/Denmark/UK/Canada/Korea (4A 18, 4B 16); ~50 PubMed records, mostly reviews + mechanistic (4C 16); Phase 3 trial registration, no approval yet (4D 5). Community Experience 30: investigational, not marketed - niche enthusiast discussion only (5A 8), <3-year track record (5B 8), limited/mixed reports (5C 7), no broad real-world tolerability signal beyond trial GI events (5D 7). Effectiveness basis clinical (moderate confidence): Phase 2 weight loss up to -16.2% vs -2.5% placebo (~14 pp placebo-adjusted), large effect far exceeding the ~5% obesity MCID, on weight/HbA1c surrogates; superior to placebo with no head-to-head vs tirzepatide/semaglutide and only one RCT, hence moderate.
MariTide represents a unique approach in the incretin-based therapy space, combining GLP-1 agonism with GIP antagonism—the opposite of tirzepatide’s dual agonist mechanism.
How It Works (Simplified)
MariTide’s bispecific design targets metabolic pathways through two distinct actions:
The GLP-1 peptide portion activates GLP-1 receptors, reducing appetite, improving glucose control, and slowing gastric emptying—standard incretin effects.
The antibody portion blocks GIP receptors, potentially reducing fat storage signals and preventing GIP-driven metabolic effects—opposite to tirzepatide.
Key Research: The peer-reviewed Phase 2 dose-ranging trial (Jastreboff et al., NEJM 2025; PMID 40549887; NCT05669599) reported up to -16.2% body weight at 52 weeks vs -2.5% with placebo in the obesity cohort, with once-monthly dosing. Topline results were first presented at ADA 2025. Amgen Press Release
Important Limitations
- GIP antagonism vs agonism debate unresolved—both approaches show efficacy
- No head-to-head trials against tirzepatide or semaglutide
- Phase 3 MARITIME program ongoing; final efficacy/safety data pending (~2027)
- Long-term cardiovascular and safety outcomes not yet established
- Currently investigational—not approved for clinical use
Once-monthly subcutaneous dosing begins, often with a lower starting dose and gradual escalation. Gastrointestinal side effects (nausea, vomiting, diarrhea) are most common during initial dosing. Early appetite suppression is typically observed.
Continued dose escalation and weight-loss trajectory. GI symptoms typically diminish as the body adjusts to the medication.
Maintenance dosing. Phase 2 data (NCT05669599) showed substantial and progressive weight loss through this period with no plateau.
Continued weight loss with curves still declining at 52 weeks. In the published Phase 2 trial, mean body-weight reduction reached up to -16.2% in the obesity (non-diabetic) cohort.
Research-based observations
This timeline reflects observations from published clinical and preclinical studies. Individual responses may vary significantly. This is not a guarantee of effects or a dosing schedule. Consult qualified healthcare providers for personalized guidance.
Good Signs (4 indicators)
Warning Signs (3 indicators)
Bad Signs (4 indicators)
For Research Evaluation Only
These quality indicators are general guidelines based on typical peptide characteristics. Professional laboratory testing (HPLC, mass spectrometry) provides definitive quality verification. This checklist is for initial visual evaluation only.
Tirzepatide
CautionBoth target GLP-1 receptors but with opposing GIP mechanisms (MariTide antagonizes, tirzepatide agonizes). Should not be combined due to overlapping primary mechanisms.
Semaglutide
CautionBoth are GLP-1 receptor agonists. Combining would result in additive GLP-1 activation and potentially severe GI adverse events. Not recommended.
Retatrutide
CautionOverlapping GLP-1 agonism and opposing GIP mechanisms. Not suitable for combination due to pharmacological conflicts.
Research Note: Interaction data is based on published literature, mechanistic understanding, and theoretical considerations. Most peptide combinations lack direct clinical study. This information is for educational purposes only and does not constitute medical advice. Always consult qualified healthcare providers.
Key Studies Cited
Full reference list available on request. All citations link to PubMed for verification.
This dossier synthesizes available evidence from peer-reviewed literature, regulatory documents, and clinical trial registries. Evidence strength ratings follow a modified GRADE approach.
For complete methodology details, see our Methodology page.
Important Disclaimer
This dossier is for educational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before making health decisions.
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