What Is MariTide (Maridebart Cafraglutide)? The Monthly Antibody–Peptide Conjugate in Phase 3

Most modern obesity medicines are built around one familiar idea:

activate GLP-1 signalling, sometimes together with another metabolic receptor.

MariTide, also known as maridebart cafraglutide and previously AMG 133, takes a much less conventional approach.

It is an antibody–peptide conjugate that:

• activates the GLP-1 receptor
• blocks the GIP receptor

rather than stimulating both receptors simultaneously.

It has also been designed for monthly or even less-frequent dosing, potentially reducing treatment frequency to only a handful of injections per year.

As of 2026, MariTide is already in a broad Phase 3 clinical programme covering obesity, type 2 diabetes, cardiovascular disease, heart failure and obstructive sleep apnoea. (Amgen⁠)

What Is MariTide?

MariTide is an investigational long-acting metabolic therapy developed by Amgen.

Its full generic name is:

maridebart cafraglutide

and it was previously known as:

AMG 133

Unlike a conventional peptide agonist, MariTide combines a peptide component with an antibody-based structure.

This is why it is described as an antibody–peptide conjugate.

What Does MariTide Target?

MariTide targets two important metabolic hormone pathways:

GLP-1 receptor activation

and

GIP receptor inhibition

This is unusual because several major metabolic medicines use the opposite GIP strategy.

Tirzepatide, for example, activates both:

• GIP
• GLP-1

MariTide instead:

• activates GLP-1
• blocks GIP signalling

That makes it one of the more scientifically distinctive programmes in current obesity research.

Why Would Researchers Block GIP?

At first glance, this may seem contradictory.

GIP receptor activation is already used successfully in dual agonists such as tirzepatide.

But biology is rarely simple.

Human genetic research has suggested that reduced GIP receptor activity may also be associated with lower body weight.

Amgen has said that genetic findings from deCODE Genetics helped guide the development strategy behind MariTide. (Amgen⁠)

This led researchers to explore whether:

GLP-1 activation + GIP receptor antagonism

could produce a useful metabolic effect.

How Does the GLP-1 Component Work?

GLP-1 signalling contributes to:

• appetite reduction
• satiety
• insulin secretion
• glucose regulation
• slower gastric emptying

This part of MariTide therefore uses a well-established metabolic pathway.

The unusual element is what happens alongside it at the GIP receptor.

What Is an Antibody–Peptide Conjugate?

MariTide is not simply a larger version of a standard GLP-1 peptide.

Its molecular design combines an antibody capable of blocking the GIP receptor with peptide-based GLP-1 receptor agonist activity.

This architecture provides two potential advantages:

dual biological action

and

very prolonged drug exposure.

The long half-life associated with the antibody component helps explain why MariTide can potentially be administered far less frequently than weekly incretin therapies.

How Often Is MariTide Given?

Current clinical programmes include once-monthly dosing.

Amgen is also investigating:

• every-eight-week dosing
• quarterly dosing

The company has stated that MariTide’s pharmacology could potentially support maintenance therapy with as few as four or six injections per year. (Amgen⁠)

This is one of its biggest potential differentiators.

What Did the Phase 2 Trial Show?

A major randomized Phase 2 trial was published in the New England Journal of Medicine in 2025.

The study included 592 participants.

Of these:

• 465 had obesity without type 2 diabetes
• 127 had obesity with type 2 diabetes

Participants received different MariTide dosing regimens or placebo for 52 weeks. (New England Journal of Medicine⁠)

How Much Weight Was Lost?

In participants with obesity without diabetes, average weight change at week 52 ranged from approximately:

–12.3% to –16.2% with MariTide

compared with:

–2.5% with placebo.

In participants with obesity and type 2 diabetes, average weight reduction ranged from approximately:

–8.4% to –12.3%

compared with:

–1.7% with placebo. (New England Journal of Medicine⁠)

Those results were strong enough to support a much larger Phase 3 development programme.

Did MariTide Affect Blood Glucose?

Yes.

In the obesity-with-diabetes cohort, average HbA1c reductions ranged from approximately:

1.2 to 1.6 percentage points

with MariTide.

The placebo group showed essentially no meaningful improvement. (New England Journal of Medicine⁠)

This indicates that the compound has effects on both:

• body weight
• glycaemic control

What Were the Main Side Effects?

Gastrointestinal adverse events were common.

These included effects typically associated with GLP-1-related therapies.

However, researchers found that gastrointestinal tolerability improved when:

• treatment started at a lower dose
• dose escalation was used

No unexpected safety signal emerged during the Phase 2 study. (New England Journal of Medicine⁠)

What Happened During the Second Year?

Amgen has also studied longer-term maintenance treatment.

Participants who had lost at least 15% of their body weight during the first year entered an exploratory second-year programme.

Amgen reported that the large majority maintained their previous weight loss while switching to:

• lower monthly doses
• or quarterly dosing

The company also reported very low rates of nausea and vomiting during the second year and no new safety signal. (Amgen⁠)

This is particularly important because long-term maintenance is becoming one of the biggest questions in obesity treatment.

Why Is Maintenance Dosing Important?

Many people regain weight after stopping effective metabolic treatment.

That creates a practical question:

Does someone need the same dose every week indefinitely?

MariTide’s development programme is testing a different model.

A patient might potentially undergo:

an initial active weight-loss phase

followed by

much less frequent maintenance dosing.

If successful, this could significantly change the long-term treatment burden.

Has MariTide Reached Phase 3?

Yes.

MariTide now has an extensive Phase 3 programme called MARITIME.

As of August 2026, ongoing studies included:

• MARITIME-1
• MARITIME-2
• MARITIME-CV
• MARITIME-HF
• MARITIME-OSA-1
• MARITIME-OSA-2
• MARITIME-SWITCH
• long-term maintenance extension studies

Additional Phase 3 studies in type 2 diabetes were also planned during 2026. (Amgen⁠)

What Is MARITIME-1?

MARITIME-1 is studying MariTide for chronic weight management in adults with obesity or overweight who do not have type 2 diabetes.

This is one of the core studies intended to confirm the weight-loss effects seen in Phase 2.

What Is MARITIME-2?

MARITIME-2 studies MariTide in adults with obesity or overweight who do have type 2 diabetes.

This population is important because weight-loss effects can differ substantially between people with and without diabetes.

What Is MARITIME-CV?

MARITIME-CV is evaluating whether MariTide influences cardiovascular outcomes.

The study is enrolling adults with:

• obesity or overweight
• established atherosclerotic cardiovascular disease

This moves the research beyond weight loss alone.

The goal is to determine whether treatment can reduce meaningful clinical outcomes such as cardiovascular events. (Amgen⁠)

What Is MARITIME-HF?

MARITIME-HF is studying people with obesity and heart failure with preserved or mildly reduced ejection fraction.

Obesity is strongly associated with this type of heart failure.

The study is investigating whether MariTide can reduce:

• heart-failure events
• cardiovascular risk

rather than simply producing weight reduction. (Amgen⁠)

What About Sleep Apnoea?

Two Phase 3 trials are investigating MariTide in people with obstructive sleep apnoea and obesity.

One includes people using positive airway pressure therapy.

The other includes people who are not using it.

This reflects growing interest in whether substantial metabolic weight reduction can improve obesity-related conditions beyond diabetes.

Can People Switch From Semaglutide or Tirzepatide?

Yes — this is specifically being studied.

The MARITIME-SWITCH Phase 3 trial is enrolling people currently using weekly:

• semaglutide
• or tirzepatide

and switching them to MariTide.

Researchers are evaluating every-eight-week and quarterly dosing schedules. (Amgen⁠)

This is particularly interesting from a real-world perspective.

Why Is Switching Research Important?

The metabolic drug market is rapidly becoming crowded.

People may eventually switch therapies because of:

• convenience
• cost
• availability
• treatment plateau
• tolerability
• preference
• maintenance needs

A drug that can replace weekly injections with treatment every two or three months could provide a significant practical advantage even if weight-loss efficacy were broadly comparable.

How Is MariTide Different From Tirzepatide?

Tirzepatide:

activates GIP + activates GLP-1

MariTide:

blocks GIP + activates GLP-1

So the compounds essentially use opposite strategies at the GIP receptor.

That makes MariTide scientifically fascinating because both approaches may potentially produce beneficial metabolic effects.

How Can Both GIP Activation and GIP Blockade Work?

This is still an active area of research.

Possible explanations involve:

• receptor desensitisation
• tissue-specific effects
• differences between chronic and acute signalling
• central nervous system effects
• interactions with GLP-1 signalling

The fact that seemingly opposite receptor strategies can both influence body weight illustrates how complex incretin biology actually is.

How Is MariTide Different From Petrelintide?

Petrelintide primarily targets the amylin pathway.

MariTide targets:

• GLP-1
• GIP receptor blockade

The mechanisms are fundamentally different.

Both are being investigated partly because researchers want alternatives to standard weekly incretin treatment.

How Is MariTide Different From Retatrutide?

Retatrutide activates:

• GLP-1
• GIP
• glucagon

MariTide:

• activates GLP-1
• blocks GIP

Retatrutide therefore attempts to increase signalling across multiple receptors.

MariTide deliberately suppresses one of those pathways.

Is MariTide a Peptide?

Partly.

MariTide is most accurately described as an antibody–peptide conjugate.

Its GLP-1 receptor agonist component is peptide-based, while the antibody architecture provides GIP-receptor antagonism and contributes to its prolonged duration of action.

So it belongs in emerging peptide therapeutics, but it is more structurally sophisticated than a conventional standalone peptide.

Is MariTide Approved?

No.

MariTide remains an investigational therapy.

Despite promising Phase 2 results and extensive Phase 3 development, it has not yet been approved for routine clinical use.

The ongoing programme still needs to establish:

• long-term effectiveness
• cardiovascular outcomes
• long-term safety
• optimal maintenance dosing
• comparative value against existing treatments

Why Is MariTide Worth Watching?

MariTide combines several unusual features:

• GLP-1 receptor agonism
• GIP receptor antagonism
• antibody–peptide engineering
• once-monthly dosing
• potential every-eight-week dosing
• potential quarterly maintenance
• cardiovascular-outcomes research
• switching studies from semaglutide and tirzepatide

Very few experimental metabolic therapies bring all of these features together.

The Bottom Line

MariTide, or maridebart cafraglutide, is an investigational long-acting antibody–peptide conjugate that combines GLP-1 receptor activation with GIP receptor blockade.

In a 592-participant Phase 2 trial, average weight reduction after 52 weeks reached up to approximately 16.2% in people without diabetes and 12.3% in people with type 2 diabetes. (New England Journal of Medicine⁠)

The programme has now expanded into multiple Phase 3 studies covering:

• obesity
• type 2 diabetes
• cardiovascular disease
• heart failure
• obstructive sleep apnoea
• treatment switching
• long-term weight maintenance. (Amgen⁠)

Perhaps its most unusual feature is its potential dosing frequency.

Amgen is investigating whether some patients can maintain results with treatment every eight weeks or even quarterly, rather than receiving an injection every week. (Amgen⁠)

That makes MariTide one of the more distinctive emerging metabolic therapies currently in Phase 3 research.

This article is for research and educational purposes only. MariTide remains investigational and is not presented as an approved or established treatment.