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%
- Human research
- 86%
Based on 14 cited sources
Numeric assessment unreviewed
A historical numeric score is recorded but has not passed a current, compound-specific assessment review. No numeric score is displayed.
This is a limitation of the numeric assessment, not a measured absence of benefit. It does not re-review the separately recorded catalogue classification or establish efficacy or safety.
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.
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
Use the source links in the research discussion above to inspect the referenced records.
This dossier synthesizes available evidence from peer-reviewed literature, regulatory documents, and clinical trial registries. Evidence strength labels summarize the cited material for this entry and should be read alongside its population, model, and study limitations.
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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Compared With
16 comparisonsConditions Studied
2 entries- MariTide for Obesity The published Phase 2 dose-ranging trial (NCT05669599; Jastreboff et al., NEJM 2025) demonstrated up to -16.2% body weight at 52 w…
- MariTide for Type 2 Diabetes In the obesity-with-type-2-diabetes cohort of the published Phase 2 trial (NCT05669599; Jastreboff et al., NEJM 2025), maridebart…