Maridebart Cafraglutide — Safety, Research, Risks & Legal Status

Not medical advice. Maridebart Cafraglutide is discussed here for informational and harm-reduction purposes only. We do not endorse use, and any dosing context is informational, not a protocol.

Also known as	AMG 133; MariTide (development brand name)
Category	GLP-1 / Metabolic
Developer	Amgen
Developmental code	AMG 133
Development brand name	MariTide
Drug class	Bispecific antibody-peptide conjugate (GIPR antagonist / GLP-1R agonist)
Dosing interval (investigational)	Once monthly subcutaneous injection
Current development stage	Phase 3 (MARITIME program); FDA approval projected no earlier than 2029-2030
US legal status	Investigational drug (United States). Not FDA-approved. No Breakthrough Therapy, Fast Track, or other special regulatory designation confirmed as of April 2026. Access is restricted to enrollment in authorized clinical trials. Not available for general clinical or consumer use.

What is Maridebart Cafraglutide?

Maridebart cafraglutide (AMG 133) is a bispecific antibody-peptide conjugate developed by Amgen for the treatment of obesity and type 2 diabetes. It consists of a fully human monoclonal antibody targeting the glucose-dependent insulinotropic polypeptide receptor (GIPR) conjugated to two GLP-1 receptor agonist peptides. The compound is designed for once-monthly subcutaneous dosing and is currently in Phase 3 clinical development under the MARITIME program.

How it works

Maridebart cafraglutide works through two simultaneous mechanisms. First, its antibody backbone antagonizes the GIP receptor (GIPR), blocking GIP signaling that is thought to contribute to adipogenesis and weight maintenance. Second, the two conjugated GLP-1 receptor agonist peptides activate GLP-1 pathways, promoting satiety, slowing gastric emptying, and improving glycemic parameters. The combined GIPR antagonism and GLP-1R agonism is hypothesized to produce synergistic metabolic effects exceeding those of GLP-1 monotherapy. Its extended terminal half-life (approximately 200-300 hours observed in preclinical species) supports once-monthly dosing, and pharmacological effects on body weight have been observed to persist for up to 150 days after the final dose in human trials.

Background & history

Maridebart cafraglutide originated from Amgen's research into bispecific antibody-based metabolic therapeutics. Early preclinical work in obese mice and cynomolgus monkeys demonstrated dose-dependent body weight reductions. Phase 1 human trials (75 participants with obesity) reported dose-dependent weight loss sustained up to 120 days after a single dose, along with improvements in fasting glucose, insulin, and lipid profiles. A Phase 2 trial published in the New England Journal of Medicine demonstrated weight loss of 12.3-16.2% in participants with obesity alone and 8.4-12.3% in those with obesity and type 2 diabetes over 52 weeks, with some cohorts approaching approximately 20% weight loss. The MARITIME Phase 3 program was initiated encompassing obesity-only, type 2 diabetes, cardiovascular, and Japan-specific trials. FDA approval is projected no earlier than 2029-2030 pending Phase 3 completion and regulatory review.

What the research says

Phase 3 development as of mid-2026 under the MARITIME program. MARITIME-1 targets adults with overweight or obesity; MARITIME-2 targets adults with type 2 diabetes and overweight or obesity; additional cardiovascular and geographic-specific trials are ongoing. Primary completion of pivotal trials is anticipated January 2027, with regulatory filing expected in 2027. Phase 2 data are published and peer-reviewed (NEJM). Phase 1 data were published in Nature Metabolism. No long-term cardiovascular outcome trial data are yet available. All human efficacy and safety data to date are derived from relatively short-duration Phase 1 and Phase 2 studies; Phase 3 results are pending.

Reported effects

Dose-dependent body weight reduction demonstrated in Phase 1 and Phase 2 human trials (up to approximately 16-20% in some Phase 2 cohorts at 52 weeks)
Improved fasting glucose and insulin levels observed in Phase 1 and Phase 2 participants
Improved lipid profiles (specific parameters not detailed in available Phase 1 summary data)
No hypoglycemic events reported in Phase 1 or Phase 2 trials
Durable weight reduction observed without apparent plateau at 52 weeks in Phase 2
Sustained pharmacological effect on body weight for up to approximately 150 days after final dose (human Phase 1 data)
Weight reductions in cynomolgus monkeys (11-13% over 6 weeks at weekly dosing) and obese mice in preclinical studies

Dosing & administration (informational)

Published Phase 1 and Phase 2 trials used subcutaneous doses ranging from 21-840 mg (single-dose escalation) and 140-420 mg administered every 4 weeks (multiple-dose cohorts). Phase 2 efficacy was demonstrated with once-monthly subcutaneous dosing. These figures are drawn from clinical trial protocols and are provided as informational context only - they do not constitute a dosing recommendation. Maridebart cafraglutide is not approved for any use outside clinical trials. Anyone interested in access should consult a licensed clinician and refer to ClinicalTrials.gov for open enrollment opportunities.

This is general research/context information, not medical advice or a recommended protocol.

Safety & side effects

Most common adverse events were gastrointestinal: nausea and vomiting, reported as mild and typically resolving within approximately 48 hours, particularly after dose escalation
No serious adverse events attributed to the drug were reported across Phase 1 or Phase 2 trials
No treatment discontinuations due to safety events reported in available Phase 1 and Phase 2 data
No unexpected safety signals identified as of Phase 2 completion
No hypoglycemia reported despite improvement in glycemic parameters
Long-term safety data (beyond 52 weeks) are not yet available; Phase 3 data pending
As with any antibody-peptide conjugate, immunogenicity (anti-drug antibodies) is a theoretical risk not fully characterized in long-term use

Drug & supplement interactions

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Who should avoid it

Use outside of authorized clinical trials (not approved, not safely characterizable outside controlled settings)
Concurrent use with other GLP-1 receptor agonists (additive or antagonistic effects not studied)
Use in individuals with a personal or family history of medullary thyroid carcinoma or MEN2 (class precaution shared with other GLP-1 agonists, not specifically studied for maridebart cafraglutide)
Use during pregnancy or lactation (no safety data available)
Combination with insulin or insulin secretagogues without medical supervision given glycemic effects
Use in pediatric populations (not studied)

How it is commonly combined

No stacking data exist. Combining maridebart cafraglutide with other GLP-1 agonists, GIP-targeting agents, or weight-loss medications has not been studied and carries unknown risk. The compound is available only in clinical trial settings where such combinations would be protocol-controlled.

Legal & regulatory. Investigational drug (United States). Not FDA-approved. No Breakthrough Therapy, Fast Track, or other special regulatory designation confirmed as of April 2026. Access is restricted to enrollment in authorized clinical trials. Not available for general clinical or consumer use.

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Frequently asked questions

How does maridebart cafraglutide differ from semaglutide or tirzepatide?

Semaglutide is a GLP-1 receptor agonist administered weekly. Tirzepatide is a dual GLP-1/GIP receptor agonist (activating both receptors) administered weekly. Maridebart cafraglutide takes a different approach: it antagonizes the GIP receptor rather than activating it, while also activating the GLP-1 receptor. This GIP antagonism/GLP-1 agonism combination is the pharmacological rationale for its development. Additionally, its antibody-based scaffold enables once-monthly rather than weekly dosing. Whether the GIP antagonism approach produces meaningfully better outcomes than GIP agonism (tirzepatide) in head-to-head trials is unknown; no comparative efficacy data have been published.

What weight loss results have been seen in human trials?

Phase 2 data published in the New England Journal of Medicine showed 12.3-16.2% body weight reduction at 52 weeks in participants with obesity (without type 2 diabetes) and 8.4-12.3% in participants with obesity and type 2 diabetes. Some reported analyses describe approximately 20% weight loss in certain Phase 2 cohorts. Phase 3 results are pending; these figures may not reflect the outcomes achievable in the broader population that Phase 3 trials are designed to characterize.

Can I get maridebart cafraglutide outside of a clinical trial?

No. As of mid-2026 maridebart cafraglutide is not approved by the FDA or any other major regulatory agency. It is available only through enrollment in Amgen's authorized MARITIME clinical trials. There is no legal commercial supply. Any product represented as maridebart cafraglutide outside of a clinical trial cannot be authenticated and should not be used.

What are the most common side effects reported so far?

Across Phase 1 and Phase 2 trials the most commonly reported adverse events were gastrointestinal: primarily nausea and vomiting. These were generally described as mild in severity and tended to resolve within approximately 48 hours, particularly following dose escalation events. No serious adverse events or treatment discontinuations due to safety were reported in available Phase 1 and Phase 2 data. Long-term safety data are not yet available and will be generated by ongoing Phase 3 trials.

What is the current clinical trial status and how do I find open trials?

The MARITIME Phase 3 program was underway as of mid-2026. Key registered trials include NCT06660173 (obesity and type 2 diabetes), NCT06987695 (Japan obesity Phase 3), and NCT07037433 (cardiovascular outcomes). Primary completion is anticipated January 2027. To find currently enrolling studies, search ClinicalTrials.gov for 'maridebart cafraglutide' or 'AMG 133' or 'MARITIME.' Eligibility criteria vary by trial.

What should I tell my doctor if I want to discuss this compound?

This page does not provide medical advice and cannot recommend a clinical approach. If you are interested in investigational weight-loss therapies, discuss your medical history, current medications, and eligibility for clinical trials with a licensed clinician familiar with obesity medicine or endocrinology. A clinician can assess whether enrolling in a MARITIME trial is appropriate and help you understand the known risks and unknowns associated with an investigational compound.

References & further reading

PubMed/Nature Metabolism: 'A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings' PMC10896721
NEJM: 'Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity - A Phase 2 Trial'
ClinicalTrials.gov: NCT06660173 (MARITIME-2, obesity + T2DM Phase 3)
ClinicalTrials.gov: NCT06987695 (Japan obesity Phase 3)
ClinicalTrials.gov: NCT07037433 (cardiovascular outcomes Phase 3)