Maridebart cafraglutide
Evidence: B+ — Meaningful Human EvidenceMetabolic / Weight Management
Evidence Snapshot
What this grade covers
Peer-reviewed discovery/Phase 1 and a full 592-participant, dual-cohort (with/without T2D) Phase 2 RCT with dual-estimand reporting, both integrity-clear. Two Phase 3 trials enrolled but not read out; immunogenicity/ADA data not yet extractable.
Regulatory Context
Maridebart cafraglutide is investigational. No approval was identified in the verified searches used for this review in any jurisdiction. Two Phase 3 trials are underway: MARITIME-1 (obesity/overweight without diabetes, NCT06858839) and MARITIME-2 (obesity/overweight with type 2 diabetes, NCT06858878); neither has reported results.
Research Takeaway
Maridebart cafraglutide (MariTide) is a long-acting peptide-antibody conjugate: a fully human monoclonal antibody that blocks (antagonizes) the GIP receptor, chemically linked to two GLP-1-receptor-agonist peptides.
Evidence boundary: Never describe this as mechanistically equivalent to Tirzepatide/VK2735 -- those are GIP-receptor AGONISTS; MariTide is a GIP-receptor ANTAGONIST conjugated to GLP-1 agonist peptides.
See all 7 evidence claims →Quick Summary
Maridebart cafraglutide (MariTide, formerly AMG 133) is a long-acting peptide-antibody conjugate: a GIP-receptor-antagonist antibody linked to two GLP-1-receptor-agonist peptides -- mechanistically opposite at the GIP receptor to tirzepatide and VK2735, which are GIP-receptor agonists. In a 592-participant Phase 2 trial, once-monthly MariTide produced substantial body-weight reduction at week 52 in adults with and without type 2 diabetes, reported under two standard trial estimands that must always be labeled separately. It is investigational, with two Phase 3 trials underway. A published scientific correspondence has raised a theoretical, hypothesis-stage question about chronic GIP-receptor antagonism and adipose-tissue biology -- this is not an observed adverse event.
Mechanism & Research Overview
Maridebart cafraglutide (MariTide) is a long-acting peptide-antibody conjugate: a fully human monoclonal antibody that is a GIP receptor ANTAGONIST, conjugated to two GLP-1 receptor AGONIST peptide analogues. This is mechanistically opposite at the GIP receptor to tirzepatide and VK2735, both of which are GIP-receptor agonists -- these must never be described as mechanistically equivalent.
Evidence Claims
Individual scientific statements drawn from the sources cited below, each shown with the specific evidence boundary that statement does not establish.
Supported
Maridebart cafraglutide (MariTide) is a long-acting peptide-antibody conjugate: a fully human monoclonal antibody that blocks (antagonizes) the GIP receptor, chemically linked to two GLP-1-receptor-agonist peptides.
Does not establish
Evidence boundary: Never describe this as mechanistically equivalent to Tirzepatide/VK2735 -- those are GIP-receptor AGONISTS; MariTide is a GIP-receptor ANTAGONIST conjugated to GLP-1 agonist peptides.
Supported
In a 592-participant Phase 2 RCT, once-monthly (or less frequent, dose-escalation-dependent) SC maridebart cafraglutide produced, under the trial's treatment-policy (intention-to-treat) analysis, mean body-weight reductions of 12.3% to 16.2% (vs 2.5% placebo) at week 52 in participants without type 2 diabetes, and 8.4% to 12.3% (vs 1.7% placebo) in participants with type 2 diabetes.
Does not establish
Evidence boundary: MANDATORY: always label this as the treatment-policy/intention-to-treat estimand; never present as the only figure -- pair with the efficacy-estimand figure (see next claim). Preferred for headline/public-summary use.
Sources: Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial
Supported
Under the same trial's efficacy (on-treatment) analysis, mean body-weight reductions reached 16.3% to 19.9% (vs 2.6% placebo) at week 52 in participants without type 2 diabetes, and 12.1% to 17% (vs 1.4% placebo) in participants with type 2 diabetes.
Does not establish
Evidence boundary: MANDATORY: always label as the efficacy/on-treatment estimand; must be presented alongside, never instead of, the treatment-policy figure. Do NOT author an unlabeled blended "up to 20%" style claim.
Sources: Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial
Supported
Gastrointestinal adverse events (nausea, vomiting, constipation, retching, diarrhea) were the main drivers of early discontinuation; in fixed, non-dose-escalation arms, 12% to 27% of participants discontinued early for GI adverse events, versus up to 7.8% in dose-escalation-schedule arms.
Does not establish
Evidence boundary: Overall (all-cause) discontinuation percentage and full AE tables were not independently extracted from full text -- do not state an overall discontinuation rate beyond the GI-specific figures given.
Sources: Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial
Supported
A published scientific correspondence has raised a theoretical hypothesis that chronic GIP-receptor antagonism could, in principle, reduce adipose-tissue de novo lipogenesis, a process associated with healthy adipose-tissue function; impaired adipose lipogenesis (as in lipodystrophy) is associated with harmful ectopic lipid accumulation in liver and muscle. This is a theoretical, hypothesis-stage discussion point, not a reported clinical finding, observed adverse event, or evidence of drug-induced lipodystrophy.
Does not establish
Evidence boundary: Must always be framed as theoretical/hypothesis-stage; never state or imply that lipodystrophy or adipose dysfunction has been observed in any MariTide trial participant.
Sources: Once-Monthly Maridebart Cafraglutide in Obesity — A Phase 2 Trial (Correspondence)
Supported
Maridebart cafraglutide is investigational; no approval was identified in the verified searches used for this review in any jurisdiction. Two Phase 3 trials are underway: MARITIME-1 (obesity/overweight without diabetes) and MARITIME-2 (obesity/overweight with type 2 diabetes); neither has reported results.
Sources: MARITIME-1: Phase 3 study of SC maridebart cafraglutide in adults with obesity/overweight without type 2 diabetes; MARITIME-2: Phase 3 study of SC maridebart cafraglutide in adults with obesity/overweight and type 2 diabetes
Supported
Anti-drug antibody (immunogenicity) testing was part of the Phase 2 trial's design; exact incidence data was not accessible for this review, and no numeric immunogenicity/anti-drug-antibody figure can currently be stated.
Does not establish
Evidence boundary: DO NOT author any numeric ADA incidence -- this claim exists only to state the evidence gap honestly.
Sources: Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial
Safety & Evidence Limitations
Considerations reported in the sources cited on this page — not a complete list of every possible risk, and not medical advice.
Safety Consideration
Gastrointestinal adverse events (nausea, vomiting, constipation, retching, diarrhea) were the main drivers of early discontinuation from the Phase 2 trial, with substantially lower discontinuation in dose-escalation-schedule arms.Safety Consideration
A published scientific correspondence has raised a theoretical hypothesis that chronic GIP-receptor antagonism could, in principle, affect healthy adipose-tissue lipid-storage function (de novo lipogenesis), by analogy to lipodystrophy-associated biology. This is a theoretical, hypothesis-stage scientific discussion, not an observed adverse event, and no MariTide trial has reported lipodystrophy or adipose dysfunction as a finding.Safety Consideration
Anti-drug-antibody (immunogenicity) testing was part of the trial's design; exact incidence data is not currently available to this project, and no immunogenicity-related safety conclusion can be drawn.
Research Areas Being Studied
Research areas discussed on this page reflect the Metabolic / Weight Management category and the sources cited below.
Findings Reported in Studies
Educational summary only — reported in cited studies, not a claim of proven benefit.
- Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial (2025):
- A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings (2024):
Study Tables by Evidence Type
Human Studies & Clinical Data
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial | 2025 | 592 participants: Cohort A obesity/overweight without T2D (n=465), Cohort B obesity/overweight with T2D (n=127) | Reports weight-loss results under TWO estimands (ICH E9(R1) framework), and BOTH must always be labeled explicitly when cited -- never blended into one unlabeled figure. TREATMENT-POLICY (intention-to-treat) ESTIMAND: Cohort A -12.3% to -16.2% vs -2.5% placebo; Cohort B -8.4% to -12.3% vs -1.7% placebo. EFFICACY (on-treatment) ESTIMAND: Cohort A -16.3% to -19.9% vs -2.6% placebo; Cohort B -12.1% to -17% vs -1.4% placebo (this on-treatment estimand range was corroborated by secondary sources, not independently confirmed against the full NEJM text). Weight loss had not plateaued at 52 weeks. HbA1c improved by -1.2 to -1.6 percentage points in Cohort B (estimand for this HbA1c figure not confirmed -- do not pair with a specific weight-loss estimand without full-text confirmation). Anti-drug-antibody/immunogenicity was a monitored secondary endpoint; exact incidence data was not accessible for this review -- ADA_NOT_EXTRACTABLE, do not author a numeric ADA claim.
| Gastrointestinal adverse events (nausea, vomiting, constipation, retching, diarrhea) were the main drivers of early discontinuation. In fixed, non-dose-escalation arms, 12% to 27% of participants discontinued early for GI adverse events, versus up to 7.8% in dose-escalation-schedule arms. Overall (all-cause) discontinuation and full AE-frequency tables were not independently extracted from full text. | |
| A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings | 2024 | Preclinical: db/db mice, DIO mice, obese cynomolgus monkeys. Human Phase 1: SAD n=49, MAD n=75 | Confirms exact molecular architecture: a fully human monoclonal antibody that is a GIP receptor ANTAGONIST, conjugated via amino-acid linkers (E384C positions) to two GLP-1 receptor AGONIST peptide analogues -- mechanistically opposite at the GIP receptor to Tirzepatide/VK2735, which are GIPR agonists. Preclinical: 11-13% weight loss over 6 weeks in monkeys. Human Phase 1: -14.5% weight change at the highest dose (420mg MAD) by day 85, durable to day 150 post-dose.
| Mild transient GI adverse events (nausea/vomiting after first dose), one transient amylase/lipase elevation, no serious adverse events or discontinuations for safety. |
Animal / Cell / Preclinical Data
No Animal / Cell / Preclinical Data Listed Yet
This section will be updated as sources are added.
Regulatory Documents & Official Trial Registries
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| MARITIME-1: Phase 3 study of SC maridebart cafraglutide in adults with obesity/overweight without type 2 diabetes | 2025 | Approximately 3,501 adults with obesity/overweight, without type 2 diabetes | Development-status only: active, not recruiting; no results yet.
| ||
| MARITIME-2: Phase 3 study of SC maridebart cafraglutide in adults with obesity/overweight and type 2 diabetes | 2025 | Approximately 1,105 adults with obesity/overweight and type 2 diabetes | Development-status only: active, not recruiting; no results yet. This will be a future source for T2D-indication efficacy data.
|
Review Articles / Secondary Sources
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Once-Monthly Maridebart Cafraglutide in Obesity — A Phase 2 Trial (Correspondence) | 2025 | N/A (theoretical/mechanistic scientific discussion, not a study population) | A published "To the Editor" letter raises a theoretical, hypothesis-stage scientific consideration: GIP receptors are abundant in adipose tissue and important for adipose-tissue de novo lipogenesis; moderate de novo lipogenesis in healthy adipose tissue has beneficial metabolic effects, whereas impaired adipose lipogenesis (as in lipodystrophy) is associated with harmful ectopic lipid accumulation in liver and muscle. The letter raises this as a mechanistic hypothesis about chronic GIP-receptor antagonism, NOT as a numerical or methodological critique of the Phase 2 trial's efficacy figures, and does not dispute any reported statistic. This must always be framed as theoretical/hypothesis-stage -- never as an observed adverse event or evidence of clinical lipodystrophy in any MariTide trial participant. |
Anecdotal Reported Patterns — Not Medical Advice
Anecdotal Reported Patterns — Not Medical Advice
Reported dosing patterns are included for educational context only. They are self-reported, unverified, not medical advice, and not instructions for human use. Community-submitted patterns are not yet available in this Phase 1 prototype; this section is a placeholder reserved for moderated, aggregated community data.
Lab Markers to Discuss With a Clinician
Educational topics only — not self-monitoring instructions.
FAQ
Disclaimer
Educational information only. This page summarizes published research and does not provide medical advice, a recommendation, or instructions for human use.
Educational use only. This content is provided for informational and research-summary purposes only. It is not medical advice, not a treatment recommendation, not a dosing guide, and not a substitute for care from a licensed medical professional. Nothing here is intended to diagnose, treat, cure, prevent, or mitigate disease. Reported dosing patterns, when shown elsewhere on the site, must be labeled either as Study / Trial Dosing or Anecdotal Reported Patterns — Not Medical Advice. Community reports are self-reported, unverified, and not scientific proof.
Community-reported experiences, once enabled, must be displayed only as moderated, anonymized, or aggregated data. They are anecdotal, self-reported, unverified, and should never be presented as proof of safety, efficacy, or expected results.
Content status: Published. Last updated .
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