Clinical Trials Pipeline & In-Development

Maridebart cafraglutide

also known as: MariTide, AMG 133, AMG-133

Amgen's once-monthly obesity injection — Phase 3 MARITIME program underway, ~20% weight loss at 52 weeks in Phase 2 (NEJM 2025), approximately 21-day half-life enabling monthly or less frequent dosing.

A first-in-class peptide-antibody conjugate developed by Amgen, consisting of a monoclonal antibody antagonist of the GIP receptor conjugated via amino-acid linkers to two GLP-1 receptor agonist peptides, delivering combined GIPR blockade and GLP-1R activation with a ~21-day plasma half-life — roughly triple that of any approved once-weekly incretin.

Mechanism of action

Unusually, maridebart cafraglutide is a GIP receptor antagonist combined with a GLP-1 receptor agonist — the opposite GIP directionality of tirzepatide (which is a GIPR agonist + GLP-1R agonist). Preclinical evidence suggests chronic GIPR blockade may improve insulin sensitivity and enhance weight loss when combined with GLP-1R agonism, though the precise biology of "GIPR agonism vs antagonism in obesity" remains one of the more contested questions in incretin pharmacology.

Primary uses

Obesity (Phase 3 investigational)
Type 2 diabetes (Phase 3 investigational)
Cardiovascular, renal, and sleep apnea indications in earlier development

Typical dosing

140–420 mg monthly or every 8 weeks (investigational) (subcutaneous)

Phase 2 tested 140, 280, and 420 mg every 4 weeks, and 420 mg every 8 weeks. Dose-escalation schedules are being optimized in Phase 3 to manage GI tolerability.

Regulatory status

Not approved. Amgen developer. Phase 3 MARITIME program is ongoing (MARITIME-1 in obesity/overweight, MARITIME-2 in type 2 diabetes) with additional Phase 3 trials in atherosclerotic cardiovascular disease, heart failure, and obstructive sleep apnea. Phase 2 results published in NEJM (Jastreboff et al., 2025; N=592) showed mean weight loss of up to 20% at 52 weeks without a weight-loss plateau. Initial Phase 3 readouts anticipated around 2027.

References

[pubmed] Jastreboff AM, et al. "Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial." N Engl J Med, 2025;393:2275.
[news-release] Amgen. "Amgen Announces Robust Weight Loss With MariTide in People Living With Obesity or Overweight at 52 Weeks in a Phase 2 Study." November 26, 2024.
[clinicaltrials] NCT06858878 — Phase 3 MARITIME-2 trial in adults with type 2 diabetes and obesity/overweight. ClinicalTrials.gov.

Related peptides

Tirzepatide

A once-weekly GLP-1/GIP dual agonist that produced unprecedented weight loss in SURMOUNT trials — up to ~21% at highest dose.

Retatrutide

An investigational triple hormone agonist that produced ~24% weight loss at 48 weeks in Phase 2 — the largest in any single-agent obesity trial to date.

Semaglutide

A once-weekly GLP-1 receptor agonist FDA-approved for type 2 diabetes and chronic weight management.

CagriSema

Novo Nordisk's next-generation obesity injection — NDA filed December 2025, FDA review expected 2026. If approved, it would be the first GLP-1 + amylin fixed-dose combination and a direct competitive response to tirzepatide.

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.