MariTide: The Once-Monthly Obesity Shot That Blocks GIP
Twelve injections a year instead of fifty-two - and a mechanism that does the exact opposite of tirzepatide on one receptor. Amgen's MariTide reached about 20% weight loss at 52 weeks with no sign of plateauing. Here is what that means.
Last updated: August 3, 2026
MariTide Is Not FDA Approved
MariTide is investigational and currently in Phase 3 trials. It is not approved, not available by prescription, and cannot legally be dispensed by any pharmacy. Because it is a monoclonal antibody conjugate rather than a simple peptide, it also cannot be meaningfully replicated by compounding - anything sold online under this name should be treated as unsafe.
Quick Answer
MariTide (maridebart cafraglutide, formerly AMG 133) is Amgen's once-monthly obesity injection - the first obesity treatment dosed monthly or less frequently. In the Phase 2 trial published in the New England Journal of Medicine, it produced up to about 20% average weight loss at 52 weeks, with mean reductions of -12.3% to -16.2% on the intent-to-treat measure and -16.3% to -19.9% on the efficacy estimand.
The headline finding is not the percentage but the shape of the curve: weight loss showed no plateau at 52 weeks, suggesting participants were still losing when the trial measurement was taken.
Its mechanism is genuinely unusual. MariTide activates the GLP-1 receptor while blocking the GIP receptor - the opposite of what tirzepatide does at GIP. It is now in Phase 3.
What Is MariTide?
MariTide is the brand-style name for maridebart cafraglutide, previously known by the development code AMG 133. It is an investigational obesity treatment from Amgen, structurally unlike anything else in the field.
Where semaglutide and tirzepatide are engineered peptides, MariTide is a bispecific antibody-peptide conjugate. Specifically, it is a fully human monoclonal antibody that antagonises the human GIP receptor, chemically conjugated via amino acid linkers to two GLP-1 receptor agonist peptide molecules.
That construction is why it behaves so differently. Monoclonal antibodies persist in the body far longer than peptides, and attaching GLP-1 peptides to an antibody backbone drags their duration of action along with it.
The GIP Paradox: Blocking vs Activating
This is the most scientifically interesting thing about MariTide, and it should be confusing if you have been following this drug class.
| Drug | GLP-1 Receptor | GIP Receptor | Weight Loss |
|---|---|---|---|
| Tirzepatide (Zepbound) | Activates | Activates | ~20-22% |
| MariTide | Activates | Blocks | ~20% |
Two drugs do opposite things at the same receptor and produce roughly similar weight loss. That is a genuine puzzle in obesity pharmacology, and researchers do not fully agree on the explanation.
The leading hypotheses:
- GIP has different effects in different tissues. GIP promotes fat storage in adipose tissue, so blocking it peripherally may reduce fat accumulation - while central GIP signalling in the brain may do something else entirely.
- Receptor desensitisation. Sustained GIP agonism may eventually downregulate the receptor, meaning long-term agonism and antagonism converge on a similar functional endpoint.
- Brain receptor involvement. Preclinical work suggests the conjugate requires both brain GIP receptors and GLP-1 receptors for its additive weight loss effect - implicating central rather than purely peripheral action.
Why this matters practically: if GIP antagonism and GIP agonism both work, they may work for different people or through partly different routes. Someone who responds poorly to tirzepatide might respond to MariTide, and vice versa. GIP receptor antagonism is being described in the endocrinology literature as an important new mechanism that expands the options available for treating obesity - not merely a variation on an existing theme.
Why Monthly Dosing Is Possible
MariTide is described as the first monthly or less frequently dosed obesity treatment, and the reason comes down to half-life. Reported at roughly 21 days, that is dramatically longer than semaglutide's week.
| Drug | Dosing | Injections Per Year |
|---|---|---|
| Saxenda (liraglutide) | Daily | 365 |
| Wegovy / Zepbound | Weekly | 52 |
| MariTide | Monthly or less | 12 or fewer |
The adherence implications are substantial. Weight regain after stopping is the central unsolved problem in this drug class, and adherence is a large part of why people stop. A treatment requiring twelve decisions a year rather than fifty-two removes a great deal of friction - particularly for people who travel, work irregular schedules, or simply find a weekly routine hard to sustain.
The flip side of a long half-life. If you react badly to a drug that persists for weeks, you cannot simply stop and wait it out - the medication remains active for a long time. That is manageable with careful dose escalation, but it is a real trade-off against the convenience, and it is the mirror image of why some patients prefer daily liraglutide.
Phase 2 Trial Results
The Phase 2 trial was published in the New England Journal of Medicine and presented at the American Diabetes Association's 85th Scientific Sessions. It enrolled participants with obesity, with and without type 2 diabetes, and ran 52 weeks.
| Measure | Result at 52 Weeks |
|---|---|
| Intent-to-treat estimand | -12.3% to -16.2% |
| Efficacy estimand | -16.3% to -19.9% |
| Headline figure | Up to ~20% average weight loss |
| 420 mg monthly dose | ~17%, without plateau |
| Obesity with type 2 diabetes | ~17% |
The two estimands measure different things and both are legitimate. The intent-to-treat figure counts everyone randomized including those who discontinued - the conservative real-world expectation. The efficacy estimand reflects participants who stayed on treatment as directed. Plan around the lower range and treat the upper as achievable with good adherence.
The result in participants with type 2 diabetes - around 17% - is notably strong. Diabetes populations consistently lose less weight on this drug class, so a relatively small gap versus the non-diabetic result is a point in MariTide's favour.
The "No Plateau" Finding
Amgen has emphasised this repeatedly, and it deserves the attention.
Most obesity medications show a characteristic curve: rapid loss in the first six to nine months, then a flattening as the body adapts and weight stabilises at a new level. That plateau is why 72-week trial results often are not dramatically better than 52-week ones.
MariTide showed no weight loss plateau at 52 weeks - participants were still losing when the trial ended. Amgen has framed this as indicating potential for further weight loss with continued treatment.
The honest caveat: "no plateau at 52 weeks" means the curve had not flattened by the time the trial stopped measuring. It does not prove weight loss continues indefinitely - every drug plateaus eventually, because the body reaches a new equilibrium. The Phase 3 program, running longer, is what will show where MariTide actually settles. Treat this as a promising signal rather than a demonstrated result.
For why plateaus happen at all, see our guide on establishing a new weight set point.
MariTide vs Approved GLP-1s
| Drug | Dosing | Weight Loss | Status |
|---|---|---|---|
| MariTide | Monthly | ~20% at 52 weeks | Phase 3 |
| Zepbound (tirzepatide) | Weekly | ~20-22% | Approved |
| Wegovy HD (7.2 mg) | Weekly | ~20.7% | Approved |
| Retatrutide | Weekly | ~28.3% at 80 weeks | Investigational |
| Amycretin | Weekly or daily oral | ~24% at 36 weeks | Investigational |
On weight loss alone, MariTide does not lead - it lands roughly where approved tirzepatide already sits. Its differentiator is the dosing schedule, not the magnitude. Whether twelve injections a year instead of fifty-two is worth choosing an investigational drug over an available one is a question Phase 3 and pricing will answer.
See also our guides to retatrutide and amycretin.
Tolerability Questions
Discontinuation rates are a live question for MariTide, and it is one of the things Phase 3 is designed to resolve.
The concern is mechanically straightforward: gastrointestinal side effects across this drug class are dose-dependent, and a monthly injection delivers a large amount of drug at once rather than spreading exposure across four weekly doses. That creates the potential for a more pronounced peak effect after each injection.
Expect the standard class side effects - nausea, vomiting, diarrhoea, constipation - with the open question being how their intensity and timing differ under monthly dosing. Amgen has explored dose escalation strategies specifically to address this, and the Phase 3 program is where the tolerability profile gets properly characterised.
What to watch for when Phase 3 reports: discontinuation due to adverse events, not overall discontinuation. Long obesity trials always lose participants for unrelated reasons. The number that matters is how many people stopped specifically because of side effects - and how that compares to the roughly 5-10% typical of weekly GLP-1s.
What to Do Now
MariTide is in Phase 3, which means years rather than months before any possible approval, with no announced date. Meanwhile approved medications already deliver comparable weight loss.
If the appeal of MariTide is adherence rather than effectiveness, that problem has partial solutions today. A weekly injection is far easier than most people expect once established - see our guide to the best place to inject tirzepatide. And if needles are the obstacle entirely, oral GLP-1s now exist: see our best oral GLP-1 comparison.
Available Now From $249/month
MariTide is years away. Physician-supervised compounded semaglutide is available today through Coreage Rx from $249/month - consultation, medication, shipping, and ongoing dose management included, no insurance required.
Frequently Asked Questions
What were the results of the MariTide Phase 2 trial?
In the Phase 2 trial published in the New England Journal of Medicine, once-monthly maridebart cafraglutide produced up to about 20% average weight loss at 52 weeks. Mean reductions were -12.3% to -16.2% on the intent-to-treat estimand and -16.3% to -19.9% on the efficacy estimand. The 420 mg monthly dose was associated with roughly 17% weight loss, and participants with obesity and type 2 diabetes lost about 17%.
How does MariTide work?
MariTide is a bispecific antibody-peptide conjugate: a fully human monoclonal antibody that blocks the GIP receptor, conjugated via amino acid linkers to two GLP-1 receptor agonist peptides. So it activates GLP-1 while antagonising GIP - the opposite of what tirzepatide does at the GIP receptor. The antibody backbone is what gives it a roughly 21-day half-life and enables monthly dosing.
Why does blocking GIP work when tirzepatide activates it?
This is an genuine open question in obesity pharmacology. Leading hypotheses include that GIP has different effects in different tissues - promoting fat storage peripherally while doing something else centrally - that sustained GIP agonism eventually desensitises the receptor so agonism and antagonism converge functionally, and that brain GIP and GLP-1 receptors are both required for the additive effect. GIP receptor antagonism is now regarded as a distinct new mechanism rather than a variation on existing ones.
When will MariTide be available?
No approval date has been announced. MariTide has advanced to Phase 3 trials after Phase 2 results. Phase 3 obesity programs typically run well over a year, followed by data analysis, regulatory submission, and review. Realistically that means years rather than months, and obesity drug timelines frequently slip.
What does "no weight loss plateau" mean?
It means participants were still losing weight when the 52-week measurement was taken, rather than the curve flattening as it typically does with most obesity drugs after six to nine months. Amgen frames this as indicating potential for further loss with continued treatment. The honest caveat is that it shows the curve had not flattened by the time the trial stopped measuring - not that weight loss continues indefinitely. Every drug plateaus eventually.
Is MariTide better than Zepbound?
Not on weight loss - both land around 20%, and they have never been compared head-to-head. MariTide's differentiator is dosing frequency: monthly or less versus weekly, meaning twelve injections a year instead of fifty-two. Zepbound is approved and available now; MariTide is investigational. For most people, an available drug beats a marginally more convenient hypothetical one.
What is the discontinuation rate of MariTide?
Tolerability is a live question that Phase 3 is designed to characterise properly. The mechanical concern is that a monthly injection delivers a large amount of drug at once rather than spreading exposure across weekly doses, which could produce a more pronounced peak in gastrointestinal side effects. When Phase 3 reports, look specifically at discontinuation due to adverse events rather than overall discontinuation, and compare it to the roughly 5-10% typical of weekly GLP-1s.
Can I get MariTide from a compounding pharmacy?
No. Beyond the fact that compounding an unapproved drug is not permitted, MariTide is a monoclonal antibody conjugate rather than a simple peptide - a fundamentally more complex biologic that cannot be meaningfully replicated by a compounding pharmacy. Anything sold online under this name should be treated as unsafe and outside any regulatory framework.
Medical Disclaimer
This article is for informational purposes only and does not constitute medical advice. MariTide (maridebart cafraglutide) is an investigational drug that has not been approved by the FDA and is not available by prescription. Nothing here should be interpreted as encouragement to obtain it from any source. Clinical trial figures come from Phase 2 studies; effect sizes and safety profiles commonly change in larger Phase 3 trials and do not predict individual results. Always consult a qualified healthcare provider before starting, stopping, or changing any medication or weight loss strategy. HealthyPound may receive compensation from affiliate partners mentioned in this article. See our affiliate disclosure and full medical disclaimer.