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MariTide: Research & Studies

Scientific evidence, clinical trials, and research findings

Evidence Level: moderate
✓Reviewed byDr. Research Team(MD (composite credential representing medical review team), PhD in Pharmacology)
📅Updated February 12, 2026
Verified

📌TL;DR

  • •2 clinical studies cited
  • •Overall evidence level: moderate
  • •8 research gaps identified
Evidence pyramid for MariTide research
Overview of evidence quality and study types

Research Studies

Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity - A Phase 2 Trial

Jastreboff AM, Ryan DH, Bays HE, et al. (2025) • New England Journal of Medicine

PubMed

Phase 2 dose-ranging trial of monthly SC MariTide in 592 participants with obesity (with and without T2D) over 52 weeks.

Key Findings

  • Up to 16.2% mean weight loss at 52 weeks in obesity without T2D
  • Up to 12.3% mean weight loss at 52 weeks in obesity with T2D
  • HbA1c reduction of 1.2-1.6 percentage points in T2D cohort
  • No weight loss plateau observed at 52 weeks
  • Monthly or less frequent dosing maintained efficacy
  • GI adverse events most common, mild to moderate, consistent with GLP-1 class
  • No new safety signals identified

Limitations: No active comparator arm52-week duration (Phase 3 will be 72 weeks)Multiple dose groups may reduce statistical power per group

A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings

Veniant MM, Lu SC, Atangan L, et al. (2024) • Nature Metabolism

PubMed

Preclinical characterization and Phase 1 clinical trial of AMG 133. Confirmed GIPR antagonist and GLP-1R agonist activities, dose-dependent weight loss, and acceptable safety profile.

Key Findings

  • Confirmed GIPR antagonist and GLP-1R agonist activities in cell-based systems
  • Reduced body weight and improved metabolic markers in obese mice and monkeys
  • Phase 1 showed acceptable safety and tolerability
  • Dose-dependent weight loss in Phase 1
  • Molecular weight confirmed at 153,514 Da
  • Half-life of approximately 21 days

Limitations: Phase 1 with small sample sizePreclinical models may not fully predict human outcomesLong-term safety not assessed

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🔍Research Gaps & Future Directions

  • •Phase 3 results from MARITIME program pending
  • •No head-to-head comparisons with tirzepatide or semaglutide
  • •Cardiovascular outcomes data not available
  • •Whether GIPR antagonism vs agonism provides different metabolic profiles long-term
  • •Effect on lean body mass preservation not fully characterized
  • •Weight maintenance after discontinuation unknown
  • •Immunogenicity data for the antibody component not fully disclosed
  • •Optimal dosing interval (monthly vs less frequent) being refined

Research Overview#

MariTide has been characterized through preclinical studies, a Phase 1 dose-finding trial (Nature Metabolism, PMID 38316982), and a Phase 2 dose-ranging trial (NEJM, PMID 40549887). As a first-in-class antibody-peptide conjugate combining GIPR antagonism with GLP-1 agonism, MariTide represents a novel approach to obesity pharmacotherapy. Phase 2 demonstrated up to 16.2% weight loss at 52 weeks with monthly dosing, leading to the Phase 3 MARITIME program.

Nature Metabolism Publication (Phase 1 + Preclinical)#

Preclinical Findings#

  • AMG 133 confirmed as GIPR antagonist and GLP-1R agonist in cell-based systems
  • Molecular weight: 153,514 Da
  • Reduced body weight and improved metabolic markers in obese mice and cynomolgus monkeys
  • Dual receptor engagement amplifies endosomal cAMP signaling

Phase 1 Clinical Results#

  • Dose-dependent weight loss
  • Half-life of approximately 21 days
  • Acceptable safety and tolerability
  • No serious safety signals

NEJM Publication (Phase 2, 52 Weeks)#

Study Design#

  • Phase 2, double-blind, randomized, placebo-controlled, dose-ranging
  • 592 participants in 11 dose groups across 2 cohorts
  • Cohort 1: Obesity without T2D
  • Cohort 2: Obesity with T2D
  • 52-week treatment period
  • Lead author: Ania M. Jastreboff (same investigator who led tirzepatide SURMOUNT trials)

Key Efficacy Results#

Cohort 1 (Obesity without T2D):

  • Up to 16.2% mean weight loss at 52 weeks at highest dose (vs 2.5% placebo)
  • No weight loss plateau at 52 weeks
  • Monthly dosing maintained efficacy

Cohort 2 (Obesity with T2D):

  • Up to 12.3% mean weight loss at 52 weeks (vs 1.7% placebo)
  • HbA1c reduction of 1.2-1.6 percentage points
  • No weight loss plateau

Safety#

  • GI adverse events were the most common, consistent with GLP-1 class
  • Most GI events were mild to moderate
  • No new safety signals identified
  • Tolerability consistent with the GLP-1 class

Phase 3 MARITIME Program#

The Phase 3 MARITIME program was informed by Phase 2 and Phase 1 PK-LDI data:

  • 72-week chronic weight management studies
  • Participants with obesity or overweight, with and without T2D
  • Dosing intervals optimized based on Phase 2 dose-response

The GIPR Antagonism vs Agonism Question#

MariTide's GIPR antagonism combined with GLP-1 agonism produces weight loss (~16%) that, while somewhat lower than tirzepatide's GIPR agonism combined with GLP-1 agonism (~21% in SURMOUNT-1), demonstrates that both approaches to GIP pathway modulation can produce meaningful weight loss. This observation suggests:

  1. The key factor may be GIP pathway modulation (either direction) rather than its direction
  2. GIPR antagonism and agonism may achieve weight loss through different downstream mechanisms
  3. Head-to-head studies will be needed to determine if one approach offers advantages

Evidence Quality Assessment#

The evidence base is moderate:

Strengths:

  • Published in NEJM and Nature Metabolism (highest-impact journals)
  • Large Phase 2 trial (592 participants, 52 weeks)
  • Novel first-in-class mechanism
  • Monthly dosing convenience
  • Both obesity and T2D data

Limitations:

  • No active comparator arm in Phase 2
  • Phase 3 results not yet available
  • No head-to-head data
  • No CV outcomes data
  • Immunogenicity of antibody component not fully characterized

Research Gaps#

  1. Phase 3 MARITIME: Pivotal trial data pending
  2. Head-to-head trials: No comparison with tirzepatide, semaglutide, or CagriSema
  3. Cardiovascular outcomes: No CVOT data
  4. GIPR antagonism vs agonism: Fundamental pharmacological question unresolved
  5. Lean mass: Effects on body composition not fully characterized
  6. Immunogenicity: Anti-drug antibody data for the antibody component
  7. Durability: Weight maintenance after discontinuation

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