Evidence memo / Metabolic & weight

MariTide

Also: maridebart cafraglutide · AMG 133 · GIPR antagonist / GLP-1 agonist

MariTide (maridebart cafraglutide) is an investigational obesity drug that blocks the GIP receptor while activating the GLP-1 receptor, designed for less frequent, possibly monthly, dosing. It is not approved. Phase 2 data have been reported, with a larger program underway. The Watchlist boundary is keeping it to its investigational obesity program and not generalizing early results.

Controlled human dataPhase 2 / Phase 3InvestigationalSafety / regulatory watch

The verdict

Our read at a glance.

Whether MariTide's GIP-receptor-blocking, GLP-1-activating approach and infrequent dosing deliver durable weight loss in larger trials and lead to approval.

The signal
Phase 2 trials have reported weight loss in obesity, and a broader program is underway. Its mechanism differs from tirzepatide, which activates GIP rather than blocking it. As an investigational drug, its full efficacy and safety remain to be established.
The unknown
Whether the GIP-antagonist approach is truly better, how tolerability and weight regain behave with infrequent dosing, and how it compares with approved and other investigational drugs.
Our read
A mechanistically distinctive investigational obesity drug, not yet proven or approved. MariTide's GIP-blocking approach and infrequent dosing are unusual, but until late-stage results and any approval it should be read as investigational.

The mechanism

How it works.

MariTide is an antibody-peptide conjugate: GLP-1-mimicking peptides are attached to an antibody that blocks the GIP receptor. The GLP-1 peptides activate their receptor in the brain and gut to reduce appetite, while the antibody body keeps the molecule in circulation long enough to allow dosing as infrequently as monthly. Blocking GIP rather than activating it (the opposite of tirzepatide) is the unusual part, and exactly how much that contributes to weight loss is still being worked out in trials.

Safety & regulatory boundary

The consequential part.

MariTide is investigational and not an approved product. Its safety profile, including gastrointestinal effects and any effects specific to GIP-receptor blockade, is still being characterized. Research-labeled or compounded versions are not an approved product, and its development status does not support use outside trials.

What's next

What we're watching.

Phase 3 obesity results, dosing-interval and weight-maintenance data, regulatory filings, and comparisons with other incretin drugs.

Context

Why this is discussed.

MariTide draws attention because it pairs an unusual mechanism (blocking GIP rather than activating it) with the prospect of monthly dosing, which would differ from the weekly incretin drugs.

The evidence base

12 cited references.

Registered trials8

Evaluating the Impact of Maridebart Cafraglutide on Cardiovascular Outcomes in Participants With Atherosclerotic Cardiovascular Disease and Overweight or Obesity

ClinicalTrials.gov · PHASE3 · RECRUITING · 2025-07-25

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

ClinicalTrials.gov · PHASE3 · RECRUITING · 2025-12-19

Maridebart Cafraglutide in Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Obesity

ClinicalTrials.gov · PHASE3 · RECRUITING · 2025-06-25

Maridebart Cafraglutide Versus Placebo in Adult Participants With Obstructive Sleep Apnea Not on Positive Airway Pressure (PAP) Therapy

ClinicalTrials.gov · PHASE3 · RECRUITING · 2025-11-25

Efficacy, Safety and Tolerability of Switching From Glucagon-like Peptide-1 Receptor Agonists (GLP-1RA) to Maridebart Cafraglutide in Adults With Obesity or Overweight (MARITIME-SWITCH)

ClinicalTrials.gov · PHASE3 · NOT_YET_RECRUITING · 2026-05-25

A Trial to Compare the Extent to Which Maridebart Cafraglutide (AMG 133) is Made Available in the Body When Administered Using Two Subcutaneous Presentations

ClinicalTrials.gov · PHASE1 · ACTIVE_NOT_RECRUITING · 2025-12-15

A Trial to Assess the Effect of Kidney Impairment on How AMG 133 is Absorbed, Broken Down, and Eliminated by the Body

ClinicalTrials.gov · PHASE1 · COMPLETED · 2025-03-11

The Effect of AMG 133 on Gastric Emptying

ClinicalTrials.gov · PHASE1 · COMPLETED · 2025-04-17

Indexed literature (PubMed)4

Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity

Drucker DJ · Diabetes Care · 2024

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

Jastreboff AM et al. · N Engl J Med · 2025

Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities

Bailey CJ et al. · Peptides · 2025

The Premise of the Paradox: Examining the Evidence That Motivated GIPR Agonist and Antagonist Drug Development Programs

Douros JD et al. · J Clin Med · 2025

Keep reading

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