How Does MariTide Work?
Understanding Amgen’s Next-Generation Obesity Drug
MariTide (maridebart cafraglutide) is an investigational weight loss drug developed by Amgen for the treatment of obesity and, in some studies, Type 2 diabetes. It represents a new direction in incretin-based medicine, combining unique engineering with convenient once-monthly dosing.
Although not yet FDA-approved, MariTide has shown strong results in early clinical trials, including notable weight reduction, improvements in body weight, and better cardiometabolic markers like blood sugar, HbA1c, and blood pressure.
But how does MariTide actually work? Let’s break it down.
MariTide’s Dual Approach: GLP-1 Activation + GIPR Antagonism
MariTide has a unique mechanism of action. While medications like Wegovy/Ozempic (semaglutide) and Mounjaro/Zepbound (tirzepatide) rely on stimulating certain hormones, MariTide takes a different, two-part approach.
MariTide activates the GLP-1 pathway
MariTide functions as a GLP-1 receptor agonist, meaning it activates the glucagon-like peptide-1 (GLP-1) receptor.
This:
- Reduces appetite
- Slows stomach emptying
- Improves insulin release
- Stabilizes blood sugar levels
These are similar GLP-1 benefits seen with semaglutide (Wegovy/Ozempic) and tirzepatide (Zepbound/Mounjaro from Eli Lilly).
MariTide blocks the GIP pathway
The second part of MariTide’s mechanism of action involves the glucose-dependent insulinotropic polypeptide (GIP) system.
MariTide acts as a GIPR antagonist, meaning it blocks the glucose-dependent insulinotropic polypeptide receptor, also called the GIP receptor.
This is different from tirzepatide, which stimulates both GLP-1 and GIP receptors as a dual receptor agonist. Instead, blocking GIP may:
- Reduce fat storage
- Enhanced weight loss and reduced body mass index (BMI)
- Offer metabolic and heart benefits
Early data suggest this GIPR-blocking approach may help the body respond differently to calories, making it easier to continue losing weight without early plateaus.
Why MariTide Lasts So Long: Antibody-Based Engineering
MariTide is built using antibody technology—a design often referred to as bispecific or antibody-peptide conjugate engineering.
This structure gives MariTide:
- An extremely long half-life
- Slow metabolic breakdown
- The potential for a monthly injection instead of frequent dosing
This long-acting design is one of the reasons experts believe MariTide could shift future weight management strategies.
What Clinical Trials Show (Phase 2 Trial Data)
In the MariTide phase 2 trial, which compared multiple dosage strengths to placebo:
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- Some groups achieved significant average weight loss, approaching levels seen with existing GLP-1 medications.
- Weight dropped by up to almost 20% when compared to their baseline level.
- People with type 2 diabetes also showed improvements of up to a 2.2 percentage point improvement in HbA1c levels and blood sugar control.
More information is available through clinicaltrials.gov, where MariTide’s endpoints, adverse events, and escalation strategies are tracked.
Moving into Phase 3
MariTide is now advancing toward Phase 3 trials, which will evaluate:
- Long-term safety
- Real-world outcomes
- Comparisons with approved agents like Zepbound, Wegovy, and Ozempic
- Effects on obstructive sleep apnea, heart failure, kidney disease, and other cardiovascular risks
Side Effects & Tolerability
Like all GLP-1-based medications, MariTide can cause gastrointestinal side effects, especially during dose escalation.
Most commonly reported include:
- Nausea
- Constipation
- Vomiting
- Stomach pain
These symptoms are similar to those seen with semaglutide, tirzepatide, and other GLP-1 receptor agonist therapies.
Thus far, findings suggest MariTide’s side-effect profile is well-tolerated and similar to other obesity medications.
How MariTide Leads to Weight Loss
The combination of GLP-1 activation and GIPR antagonism produces several metabolic benefits:
- Appetite suppression
- Slower gastric emptying
- Improved glucose regulation
- Reduced caloric intake
- Potential reduction in fat storage
- Improvements in cardiometabolic markers
These effects help people lower their body weight, improve BMI, and enhance overall healthcare outcomes when used as part of a weight management plan.
The Bottom Line: How MariTide Works
MariTide works by combining two powerful actions:
- Activating the GLP-1 receptor
- Blocking the GIP receptor (GIPR antagonism)
This dual approach may offer:
- Significant weight loss
- Improved blood sugar control
- Better cardiometabolic health
- Convenient monthly injection
Although more data is needed from ongoing and future Phase 3 trials, early results suggest MariTide could become a major new option in the obesity drug landscape once evaluated by the Food and Drug Administration and other global regulators.
Sources
- Jastreboff, A. M., et al. MariTide Phase 2 Obesity Trial Investigators (2025). Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity – A Phase 2 Trial. The New England Journal of Medicine. DOI: 10.1056/NEJMoa2504214. Accessed Nov. 25, 2025.
- AMGEN ANNOUNCES ROBUST WEIGHT LOSS WITH MARITIDE IN PEOPLE LIVING WITH OBESITY OR OVERWEIGHT AT 52 WEEKS IN A PHASE 2 STUDY. (2024, November 26). Amgen. Accessed Nov. 25, 2025.