MariTide: The Monthly Weight Loss Injection That Keeps Working After You Stop

Every week, millions of patients around the world inject themselves with a GLP-1 medication. Every week, for months or years. What if you only had to do it once a month?

Amgen's MariTide (maridebart cafraglutide) is a first-in-class antibody-peptide conjugate designed for monthly dosing. In Phase 2 trials published in the New England Journal of Medicine, it produced approximately 20% weight loss at 52 weeks with once-monthly injections. That is comparable to what weekly tirzepatide (Zepbound) achieves at its approved dose.

But the dosing frequency is only part of the story. MariTide's structure gives it a half-life of roughly 21 days, about three times longer than any approved weekly GLP-1 drug. In Phase 1 data, participants maintained an 11.2% weight reduction for up to 150 days (five months) after their last dose. No rapid weight regain. No rebound. That is a sharp contrast to what happens when patients stop semaglutide or tirzepatide, where weight typically returns within months.

MariTide entered Phase 3 trials in early 2025. Here is what the data shows and when patients might have access to it.

How MariTide works

MariTide is structurally unlike any other obesity drug in development. It is an antibody-peptide conjugate: a fully human monoclonal antibody with two GLP-1 receptor agonist peptides chemically attached to it via amino acid linkers.

The antibody component blocks GIP receptors (GIP antagonism). The peptide components activate GLP-1 receptors (GLP-1 agonism). This gives MariTide a dual mechanism:

GLP-1 receptor agonism suppresses appetite, signals satiety, slows gastric emptying, and improves blood sugar control. Same pathway as semaglutide and tirzepatide.

GIP receptor antagonism blocks GIP signalling, which may reduce fat storage. This is the opposite of what tirzepatide does, which activates GIP receptors. Paradoxically, both approaches appear to produce comparable weight loss. The science behind why both GIP agonism and GIP antagonism lead to similar outcomes is still being studied.

The antibody structure gives MariTide its key practical advantage: a plasma half-life of approximately 21 days. For comparison, semaglutide's half-life is about 7 days. This extended half-life is what enables monthly dosing and the unusual weight maintenance signal seen after stopping.

Phase 2 results

The Phase 2 trial (NCT05669599) was published in the New England Journal of Medicine in June 2025. It enrolled 592 adults across two groups.

Weight loss in patients without type 2 diabetes (n=465)

Participants received monthly fixed doses (140 mg, 280 mg, or 420 mg), an 8-week 420 mg arm, or dose-escalation arms starting at 70 mg.

• Mean weight loss at 52 weeks: 12.3% to 16.2% across dose groups (vs 2.5% with placebo)
• Best-performing dose-escalation arm: approximately 20% weight loss
• Weight loss had not plateaued at 52 weeks

Weight loss in patients with type 2 diabetes (n=127)

• Mean weight loss at 52 weeks: 8.4% to 12.3% (vs 1.7% with placebo)
• HbA1c reduction: up to 2.2 percentage points
• Improvements in blood pressure, waist circumference, BMI, and inflammatory markers

More than 90% of eligible Phase 2 participants chose to continue into the extension phase, a strong signal that patients found the treatment acceptable.

Body composition

The trial measured body composition via DXA scanning. Amgen reported a favourable ratio of fat loss to lean mass preservation, meaning more of the weight lost was fat rather than muscle. There was no association between MariTide and bone mineral density changes.

(An earlier Phase 1 concern about a possible 4% bone density drop at the highest 420 mg dose was not replicated in Phase 2.)

Weight maintenance after stopping

This is MariTide's most distinctive data point.

In Phase 1 data, participants maintained an 11.2% weight reduction for approximately 150 days (five months) after their last dose of MariTide. Maximum weight loss was maintained for about two months after stopping, with only gradual, partial regain over the following months.

Compare this to what happens when patients stop semaglutide. The STEP 1 extension study showed approximately two-thirds of weight regain within one year of stopping treatment. Patients go from their maintenance weight back toward their starting weight relatively quickly once the drug clears their system.

The explanation is pharmacokinetic. MariTide's 21-day half-life means the drug is still active in your body for weeks after the last injection. Instead of an abrupt drop-off (as with weekly GLP-1 drugs that clear within 2-3 weeks), MariTide provides a gradual taper. The antibody component of the molecule persists even longer than typical peptide drugs.

Phase 2 Part 2 (ongoing) is specifically testing this question. Cohorts were re-randomised to placebo, lower monthly doses, or quarterly dosing (420 mg every 12 weeks) to see whether weight can be maintained with less frequent injections. Results have not been published yet.

If MariTide enables quarterly maintenance dosing, that would mean just four injections per year to sustain weight loss. That would be a significant shift from the current paradigm of indefinite weekly treatment.

The convenience factor

For patients considering weight loss treatment, the injection frequency matters. It is easy to underestimate how much a weekly injection affects daily life, especially over months or years of treatment.

MariTide reduces the injection burden from 52 times a year to 12. During a potential maintenance phase, it could be as few as 4. It is delivered through a patient-friendly autoinjector device, similar in concept to the pens used for weekly medications but taken less often.

This matters most for:

Adherence. Fewer injections means fewer chances to miss a dose. Medication adherence tends to decline with more frequent dosing requirements.

Travel. Weekly injections require carrying medication and maintaining cold storage while travelling. Monthly dosing means dealing with this far less often.

Psychological burden. Some patients find the weekly injection routine manageable. Others find it a constant reminder. Monthly dosing reduces this friction.

Side effects

The side effect profile is consistent with the GLP-1 class. Gastrointestinal events (nausea, vomiting, constipation) were the most common adverse effects.

The Phase 2 trial showed that dosing strategy dramatically affects tolerability:

The lesson from Phase 2 was clear: starting at a high dose without escalation caused severe GI events, but gradual dose escalation with an optimised schedule nearly eliminated treatment discontinuation. The Phase 3 programme uses an 8-week dose escalation starting at 21 mg, based on these tolerability findings.

More than 90% of MariTide-treated patients experienced at least one adverse event (vs 68-81% on placebo), but GI events were predominantly mild, transient, and primarily associated with the first dose. No injection site reactions were significantly different from placebo.

Phase 3: the MARITIME programme

Amgen launched six Phase 3 studies in 2025 under the MARITIME (MARITide In MEtabolic disease) programme:

The Phase 3 target doses are significantly lower than the highest Phase 2 doses. While Phase 2 tested up to 420 mg monthly, the Phase 3 programme starts at 21 mg and escalates over 8 weeks. This reflects Amgen's revised strategy after finding that dose escalation at lower doses achieved comparable efficacy with far better tolerability.

How MariTide compares

MariTide's weight loss may not match the absolute numbers from retatrutide or amycretin. But its competitive advantages are different: monthly dosing, potential quarterly maintenance, and weight durability after stopping. These are practical benefits that affect real-world adherence and patient experience, not just clinical trial efficacy numbers.

What this means for Singapore patients

MariTide is not available and will not be for several years. Phase 3 results are expected in early 2027, with potential FDA approval around 2029-2030. Singapore's HSA typically reviews 12-24 months after FDA, placing local availability around 2030-2032.

For patients in Singapore today, effective GLP-1 treatments are available now. Trimly prescribes both injectable semaglutide (Wegovy) and oral semaglutide (Rybelsus), along with tirzepatide. Weekly injections are the current standard, and for most patients, they become routine after the first few weeks.

If weekly injections are the main barrier, the oral Rybelsus option removes the needle entirely, though it requires daily dosing with fasting requirements.

Frequently asked questions

What is MariTide?

MariTide (maridebart cafraglutide) is a first-in-class antibody-peptide conjugate developed by Amgen. It combines GLP-1 receptor agonism with GIP receptor antagonism in a single molecule, with a long half-life that enables once-monthly dosing. It is currently in Phase 3 trials.

How often do you inject MariTide?

Once a month in the current trials. Phase 2 extension data is testing whether quarterly dosing (every 12 weeks) is sufficient for weight maintenance, which would mean just 4 injections per year.

How much weight loss does MariTide produce?

The Phase 2 trial showed approximately 20% weight loss at 52 weeks with the best-performing dose-escalation regimen. Weight was still declining at 52 weeks, suggesting further loss with longer treatment.

Does weight come back after stopping MariTide?

Phase 1 data showed participants maintained an 11.2% weight reduction for up to 150 days after their last dose, with only gradual partial regain. This is significantly better than what is seen with weekly GLP-1 drugs, where most weight returns within a year of stopping.

When will MariTide be available?

Phase 3 results are expected in early 2027. If successful, FDA approval could come around 2029-2030. Singapore availability would likely follow in 2030-2032.

The bottom line

MariTide offers a different kind of progress in obesity treatment. Its approximately 20% weight loss is comparable to current approved weekly medications, not significantly better. What sets it apart is how that treatment is delivered: monthly instead of weekly, with early data suggesting weight can be maintained for months after stopping.

If Phase 3 confirms these advantages, MariTide could change the practical experience of obesity treatment from an indefinite weekly commitment to a less intensive, more sustainable routine.

It is years from being available. But the concept of less frequent dosing with durable effect is a real step forward for patients who need long-term treatment but find weekly injections difficult to maintain indefinitely.

MariTide (maridebart cafraglutide) is an investigational drug not approved by any regulatory authority. The clinical trial results discussed are from published peer-reviewed studies but may not reflect final outcomes. Weight loss results vary by individual. This article is for informational purposes only and does not constitute medical advice. Consult your doctor before starting any medication. Trimly is a MOH-licensed telehealth clinic (HCSA License R/25M0505/MDS/001/252).