Metabolic/Weight

Maridebart Cafraglutide

Research Reagent · Laboratory Use Only

Quick Answer

What does research show about MariTide (maridebart cafraglutide) for weight loss?

Maridebart cafraglutide (MariTide, AMG 133) is Amgen's once-monthly peptide-antibody conjugate combining GLP-1 receptor agonism with GIP receptor antagonism. In the Phase 2 MARITIME-1 trial (New England Journal of Medicine, June 2025), participants without diabetes lost up to approximately 20% of body weight at 52 weeks versus 2.6% with placebo, without plateauing. The Phase 3 MARITIME program, comprising six global trials, is underway and expected to run through January 2027.

PMID40549887↗DOI10.1056/NEJMoa2504214↗⟳ Reconstitution Calculator
Scientific AbstractPMID 40549887 · 2025

Maridebart cafraglutide (AMG 133; brand-track name MariTide) is a long-acting peptide-antibody conjugate developed by Amgen that combines GLP-1 receptor agonism with GIP receptor antagonism, administered by monthly (or less frequent) subcutaneous injection. In the Phase 2 MARITIME-1 trial (New England Journal of Medicine, June 2025; PMID 40549887), 592 adults with obesity or overweight (465 without diabetes, 127 with type 2 diabetes) were randomized to placebo or maridebart cafraglutide across a dose-ranging design. 2 percentage points.

Amgen initiated the Phase 3 MARITIME program in 2026, comprising six global trials: MARITIME-1 (NCT06858839, obesity/overweight without diabetes), MARITIME-2 (NCT06858878, obesity/overweight with type 2 diabetes), plus additional Phase 3 studies evaluating cardiovascular outcomes (NCT07037433), obstructive sleep apnea (NCT07225686), elevated liver fat (NCT07441252), and a Japan-specific obesity study (NCT06987695). The Phase 3 program is expected to run through January 2027.

Source:10.1056/NEJMoa2504214
Mechanistic Research SummaryCurated from PubMed

This data is for laboratory research purposes only. Not for human or animal consumption.

What is Maridebart Cafraglutide (MariTide)?

Maridebart cafraglutide (development code AMG 133, commonly referred to by the working name MariTide) is a long-acting peptide-antibody conjugate developed by Amgen for obesity and related metabolic conditions. Its distinguishing feature is a dosing interval of once monthly or less frequently, made possible by fusing GLP-1 receptor-agonist peptides to an antibody fragment that extends circulating half-life.

Mechanism of Action

Maridebart cafraglutide combines two mechanisms in a single molecule: GLP-1 receptor agonism, which suppresses appetite and slows gastric emptying, and GIP receptor antagonism, a mechanistically distinct approach from GIP-agonist peptides like tirzepatide. The antibody-conjugate backbone extends the drug's half-life to roughly three weeks, enabling monthly dosing intervals uncommon among peptide-class metabolic therapeutics.

Observed Clinical Results

  • Phase 2 MARITIME-1 (NEJM, June 2025; PMID 40549887, NCT05669599): 592 participants; up to ~20% weight loss at 52 weeks in obesity without diabetes (vs 2.6% placebo), up to ~17% in obesity with type 2 diabetes (vs 1.4% placebo); HbA1c reductions up to 2.2 percentage points; weight loss had not plateaued by week 52.
  • Phase 3 MARITIME-1 (NCT06858839): Obesity/overweight without type 2 diabetes; ongoing.
  • Phase 3 MARITIME-2 (NCT06858878): Obesity/overweight with type 2 diabetes; ACTIVE_NOT_RECRUITING; primary completion estimated January 2027.
  • Additional Phase 3 expansion studies: Cardiovascular outcomes (NCT07037433), obstructive sleep apnea (NCT07225686), elevated liver fat/MASLD (NCT07441252), and a Japan obesity study (NCT06987695).

Regulatory Status

Investigational — no regulatory approval as of June 2026. Phase 3 MARITIME program ongoing across six global trials, expected to run through January 2027. As a peptide-antibody conjugate biologic, not eligible for 503A compounding.

Clinical Research Parameters
6 trials1 human study

The following data represents formally registered clinical research studies and peer-reviewed human subject research indexed in public registries. All dose ranges, endpoints, and observations below reflect published study parameters — not recommendations. For research reference only.

Registered Clinical Trials
ClinicalTrials.gov ↗
NCT05669599 ↗
COMPLETEDPhase IIn=592

A Study to Evaluate the Efficacy and Safety of AMG 133 (Maridebart Cafraglutide) in Adult Participants With Obesity or Overweight (MARITIME-1 Phase 2)

Phase 2, randomised, double-blind, placebo-controlled, dose-ranging trial evaluating once-monthly (or less frequent) subcutaneous maridebart cafraglutide in 592 adults across two cohorts: obesity/overweight without diabetes (n=465) and obesity/overweight with type 2 diabetes (n=127). Published in the New England Journal of Medicine (June 2025, PMID 40549887): participants without diabetes lost up to approximately 20% of body weight at 52 weeks (vs 2.6% placebo) with no plateau observed; participants with type 2 diabetes lost up to approximately 17% (vs 1.4% placebo) with HbA1c reductions of up to 2.2 percentage points. Dose-escalation regimens reduced gastrointestinal discontinuation rates (8% vs 12-17% without escalation).

Study Interventions
Maridebart cafraglutide 140/280/420 mg (various regimens), Placebo
Primary Endpoints
Percent change in body weight from baseline at week 52
Study Period
2023-01 → 2025-03
NCT06858839 ↗
ACTIVE NOT RECRUITINGPhase III

A Study of Maridebart Cafraglutide in Adult Participants With Obesity or Overweight (MARITIME-1 Phase 3)

Phase 3, randomised, double-blind, placebo-controlled trial evaluating maridebart cafraglutide for weight management in adults with obesity or overweight without type 2 diabetes, using lower starting doses (21 mg escalating to 35 mg then 70 mg over 8 weeks) than the Phase 2 study. Part of Amgen's six-trial global MARITIME Phase 3 program.

Study Interventions
Maridebart cafraglutide, Placebo
Primary Endpoints
Percent change in body weight from baseline
Study Period
2025-02 → 2027-01
NCT06858878 ↗
ACTIVE NOT RECRUITINGPhase III

Efficacy and Safety of Maridebart Cafraglutide in Adult Participants With Type 2 Diabetes Mellitus Who Have Obesity or Are Overweight (MARITIME-2)

Phase 3, randomised, double-blind, placebo-controlled study evaluating the efficacy, safety, and tolerability of maridebart cafraglutide in adults with type 2 diabetes who have obesity or are overweight. Primary completion estimated January 21, 2027.

Study Interventions
Maridebart cafraglutide, Placebo
Primary Endpoints
Percent change in body weight from baseline; Change in HbA1c from baseline
Study Period
2025-03 → 2027-01
NCT07037433 ↗
RECRUITINGPhase III

Evaluating the Impact of Maridebart Cafraglutide on Cardiovascular Outcomes in Participants With Atherosclerotic Cardiovascular Disease and Overweight or Obesity (MARITIME-3)

Phase 3, event-driven cardiovascular outcomes trial evaluating whether maridebart cafraglutide reduces major adverse cardiovascular events in adults with established atherosclerotic cardiovascular disease and overweight or obesity. Part of Amgen's expanded MARITIME Phase 3 program beyond weight management.

Study Interventions
Maridebart cafraglutide, Placebo
Primary Endpoints
Time to first occurrence of major adverse cardiovascular event (MACE)
Study Period
2025-09 → 2029-12
NCT07225686 ↗
RECRUITINGPhase III

Maridebart Cafraglutide Versus Placebo in Adult Participants With Obstructive Sleep Apnea on Positive Airway Pressure Therapy

Phase 3 trial evaluating maridebart cafraglutide versus placebo in adults with obstructive sleep apnea and obesity who are on positive airway pressure therapy, assessing whether weight reduction improves apnea-hypopnea index and related outcomes.

Study Interventions
Maridebart cafraglutide, Placebo
Primary Endpoints
Change in apnea-hypopnea index (AHI) from baseline
Study Period
2025-11 → 2028-06
NCT07441252 ↗
RECRUITINGPhase III

A Trial to Evaluate Efficacy and Safety of Maridebart Cafraglutide in Adults Living With Elevated Liver Fat and Obesity or Overweight

Phase 3 trial evaluating maridebart cafraglutide in adults with elevated liver fat (MASLD) and obesity or overweight, assessing effects on liver fat content alongside weight loss.

Study Interventions
Maridebart cafraglutide, Placebo
Primary Endpoints
Change in liver fat content from baseline (MRI-PDFF)
Study Period
2026-02 → 2028-03
Research Compliance Notice

All data presented on this page is for laboratory research purposes only. Maridebart Cafraglutide is referenced here as a research reagent. This page does not constitute medical advice, clinical guidance, or endorsement of any compound for human or animal use. All referenced studies are available via PubMed (PMID: 40549887) and the DOI-linked journal publication. Researchers must consult applicable institutional and regulatory frameworks before conducting any protocols.

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