Maridebart Cafraglutide
Also known as: AMG 133, MariTide
Antibody-peptide conjugate; bispecific molecule combining a fully human monoclonal anti-human GIPR antagonist antibody conjugated to two GLP-1 analogue agonist
What it is
Maridebart cafraglutide (AMG 133 / MariTide) is a long-acting peptide-antibody conjugate that simultaneously activates glucagon-like peptide-1 receptors (GLP-1R agonism) and blocks glucose-dependent insulinotropic polypeptide receptors (GIPR antagonism) (PMID 40549887; PMID 38316982). It is engineered by conjugating a fully human monoclonal anti-human GIPR antagonist antibody to two GLP-1 analogue agonist peptides using amino acid linkers, decoupling peptide synthesis from antibody expression and enabling incorporation of non-proteinogenic amino acids and other chemical features that enhance peptide stability, potency, and half-life. GIPR agonism and antagonism have both paradoxically shown significant weight loss effects in humans when combined with GLP-1R agonism (PMID 41287212; PMID 40507574). The antibody scaffold extends the plasma half-life relative to peptide-only approaches, supporting a once-monthly dosing schedule (PMID 41054801; PMID 41948476).
Class: Antibody-peptide conjugate; bispecific molecule combining a fully human monoclonal anti-human GIPR antagonist antibody conjugated to two GLP-1 analogue agonist peptides via amino acid linkers
What it's studied for
- Obesity (weight reduction without type 2 diabetes) Human RCT
- Phase 2 double-blind RCT in participants with obesity (n=465 in obesity cohort; mean BMI 37.9): mean percent change in body weight from baseline to week 52 ranged from -12.3% (95% CI -15.0 to -9.7) to -16.2% (95% CI -18.9 to -13.5) with maridebart cafraglutide, vs -2.5% (95% CI -4.2 to -0.7) with placebo. Gastrointesti PMID 40549887 Jastreboff AM et al. Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity - A Phase 2 Trial. N Engl J Med. 2025.
- Obesity with type 2 diabetes (weight reduction and glycemic control) Human RCT
- Phase 2 double-blind RCT in obesity-diabetes cohort (n=127; mean BMI 36.5): mean percent change in body weight from baseline to week 52 ranged from -8.4% (95% CI -11.0 to -5.7) to -12.3% (95% CI -15.3 to -9.2) with maridebart cafraglutide vs -1.7% (95% CI -2.9 to -0.6) with placebo. Mean change in HbA1c: -1.2 to -1.6 p PMID 40549887 Jastreboff AM et al. Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity - A Phase 2 Trial. N Engl J Med. 2025.
- Obesity (phase 1 dose-ranging, safety, tolerability, and weight loss) Human RCT
- Phase 1 randomized, double-blind, placebo-controlled clinical study in participants with obesity (NCT04478708): AMG 133 had an acceptable safety and tolerability profile along with pronounced dose-dependent weight loss. In multiple ascending dose cohorts, weight loss was maintained for up to 150 days after the last dos PMID 38316982 Véniant MM et al. A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings. Nat Metab. 2024.
- Reduction of body weight and improvement of metabolic markers (preclinical: obese mice and cynomolgus monkeys) Animal studies only
- AMG 133 reduced body weight and improved metabolic markers in male obese mice and cynomolgus monkeys. GIPR antagonist and GLP-1R agonist activities were confirmed in cell-based systems. PMID 38316982 Véniant MM et al. A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings. Nat Metab. 2024.
Community-reported dosing
| Route | Dose | Frequency / Duration | Population / context | Source tier |
|---|---|---|---|---|
| Subcutaneous injection | 140 mg, 280 mg, or 420 mg subcutaneously every 4 weeks (without dose escalation); 420 mg every 8 weeks (without dose escalation); 420 mg every 4 weeks with 4-week dose escalation; 420 mg every 4 weeks with 12-week dose escalation | 52 weeks | human | Research PMID 40549887 |
| Not specified in abstract | Multiple ascending doses (specific doses not stated in abstract) | Up to 150 days of follow-up after last dose | human | Research PMID 38316982 |
Tier key: Research = PMID-cited study · [C] = scraped community source · [S] = model-synthesized from aggregate community reports (softer evidence). How we source.
Safety signals
- Gastrointestinal adverse events were common with maridebart cafraglutide; frequency was lower with dose escalation strategies and lower starting doses PMID 40549887
- In the phase 1 study, AMG 133 had an acceptable safety and tolerability profile; no specific adverse events are described beyond this general characterization in the abstract PMID 38316982
- In obese mice, GIPR antagonism (analogous to the mechanism of maridebart cafraglutide) reduced insulin sensitivity compared to pair-fed controls and slightly increased liver triglyceride content PMID 41287212
Frequently asked
What is maridebart cafraglutide (MariTide / AMG 133) and how does it work?
Maridebart cafraglutide (also known as AMG 133 or MariTide) is a long-acting antibody-peptide conjugate that combines GLP-1 receptor agonism with GIP receptor antagonism in a single molecule. It is engineered by attaching two GLP-1 analogue peptides to a fully human anti-GIPR monoclonal antibody via amino acid linkers, which extends its half-life and enables once-monthly dosing (PMID 42592044; PMID 40549887; PMID 38316982).
How much weight loss can I expect with maridebart cafraglutide?
In a phase 2 RCT (52 weeks), adults with obesity (without type 2 diabetes) lost a mean of -12.3% to -16.2% of body weight, compared to -2.5% with placebo. Adults with obesity and type 2 diabetes lost a mean of -8.4% to -12.3% vs -1.7% with placebo. These are group-level results from a clinical trial and individual results vary. I'm not a medical professional and can't predict what results you personally would experience.
What dose of maridebart cafraglutide should I take?
I'm not a medical professional and can't recommend a protocol for you specifically. What research has shown: in a phase 2 trial, doses of 140 mg, 280 mg, or 420 mg were given subcutaneously every 4 weeks, and 420 mg every 8 weeks, with or without dose escalation schedules, over 52 weeks. Dosing decisions require evaluation by a licensed healthcare provider.
Is maridebart cafraglutide FDA-approved?
The reviewed scientific literature does not explicitly state the current FDA approval status of maridebart cafraglutide. The compound has been studied through phase 1 and phase 2 clinical trials, with the phase 2 trial funded by Amgen. For current regulatory status, please consult the FDA website or a licensed healthcare provider — requires manual verification.
What are the side effects of maridebart cafraglutide?
In the phase 2 trial, gastrointestinal adverse events were the most commonly reported side effects. They were less frequent when a dose escalation strategy or lower starting dose was used. No unexpected safety signals emerged in that 52-week trial. In the phase 1 study, the drug had an acceptable safety and tolerability profile. Long-term safety data beyond 52 weeks are not available in the reviewed literature.
How is maridebart cafraglutide different from tirzepatide (Mounjaro/Zepbound)?
Both drugs target the GIP and GLP-1 systems, but through opposite mechanisms at the GIP receptor: tirzepatide is a GLP-1R/GIPR dual agonist (activates both receptors), while maridebart cafraglutide is a GLP-1R agonist combined with a GIPR antagonist (blocks the GIP receptor). Paradoxically, both approaches have shown significant weight loss in clinical studies (PMID 42166683; PMID 41287212; PMID 40507574). Additionally, maridebart cafraglutide is an antibody-peptide conjugate designed for once-monthly dosing, whereas tirzepatide is a peptide administered weekly (PMID 40549887; PMID 42592044).
Can I use maridebart cafraglutide with semaglutide or other GLP-1 agonists?
I can't recommend combining compounds — that's a prescribing decision. Here's what has been studied individually: maridebart cafraglutide has been studied as a standalone agent in phase 1 and phase 2 trials. No combination studies with semaglutide or other GLP-1 agonists are described in the reviewed literature.
Does maridebart cafraglutide help with type 2 diabetes control?
In the phase 2 RCT, participants with obesity and type 2 diabetes who received maridebart cafraglutide experienced mean HbA1c reductions of -1.2 to -1.6 percentage points, compared to +0.1 percentage points in the placebo group. These are research findings; I can't suggest treatments for medical conditions. Please speak with a licensed healthcare provider.
Where can I buy maridebart cafraglutide?
I don't recommend vendors or sources. Please consult a licensed provider.
How long do the weight loss effects of maridebart cafraglutide last after stopping?
In the phase 1 multiple ascending dose cohorts, weight loss was maintained for up to 150 days after the last dose. The phase 2 trial measured outcomes at 52 weeks of treatment. Data on weight regain after discontinuation beyond these timepoints are not available in the reviewed literature. I don't have reliable study data on that specific question beyond what is cited — please consult a licensed provider or peer-reviewed literature directly.
References
- [1] PMID 40549887 — Phase 2 double-blind RCT in participants with obesity (n=465 in obesity cohort; mean BMI 37.9): mean percent change in body weight from baseline to week 52 rang
- [2] PMID 38316982 — Phase 1 randomized, double-blind, placebo-controlled clinical study in participants with obesity (NCT04478708): AMG 133 had an acceptable safety and tolerabilit
- [3] PMID 41287212 — In obese mice, GIPR antagonism (analogous to the mechanism of maridebart cafraglutide) reduced insulin sensitivity compared to pair-fed controls and slightly in
- [4] PMID 42592044 — in-prose reference
- [5] PMID 40507574 — in-prose reference
- [6] PMID 41054801 — in-prose reference
- [7] PMID 41948476 — in-prose reference
- [8] PMID 42166683 — in-prose reference