MariTide (Maridebart Cagrilintide): Amgen's Monthly Obesity Drug Reviewed (2026)

Last updated: June 2026

Medical disclaimer: This article is for informational purposes only and is not medical advice. MariTide (maridebart cagrilintide) is an investigational drug and is not FDA-approved as of 2026. Do not start, stop, or change any treatment based on what you read here. Consult your doctor.

MariTide is Amgen's investigational obesity drug, also known by its research code AMG 133 and its generic name maridebart cafraglutide. It stands out for two reasons: a once-monthly shot and a mechanism that blocks the GIP receptor rather than turning it on. This review pulls the real numbers from the Phase 1 and Phase 2 trials, with every figure tied to a primary source.

A quick naming note. The drug's official generic name is maridebart cafraglutide. You will also see it written as "maridebart cagrilintide" in some early coverage, but both labels point to the same molecule, AMG 133.

What is MariTide and how does its GIP-antagonist mechanism work?

MariTide is a long-acting peptide-antibody conjugate that activates the GLP-1 receptor while blocking the GIP receptor. That GIP-blocking design is the counterintuitive part, and it is why MariTide is so different from the approved drugs.

Most obesity drugs activate receptors. Semaglutide (Ozempic, Wegovy) turns on GLP-1. Tirzepatide (Mounjaro, Zepbound) turns on both GLP-1 and GIP. MariTide turns on GLP-1 but turns off GIP (Nature Metabolism, 2024).

How is it built? Amgen attached a fully human antibody that blocks the GIP receptor to two GLP-1 agonist peptides, joined by amino-acid linkers (Nature Metabolism, 2024).

The antibody piece is the trick behind monthly dosing. Antibodies clear from the body slowly, so the whole molecule lingers for weeks instead of days.

Here is the puzzle. Tirzepatide activates GIP and works well, yet MariTide blocks GIP and also works well. How can both directions help weight loss?

The leading idea is that what matters is sustained signaling, not direction. Chronically blocking GIP may desensitize the pathway in a way that mimics what chronic activation does (Nature Metabolism, 2024).

The half-life numbers explain the dosing schedule. The intact molecule has a half-life of about 14 to 16 days, and the total drug stretches to 21 to 24 days (Nature Metabolism, 2024).

That long tail is why MariTide can be given as a shot under the skin once a month, or even less often. You can see where it sits among newer drugs in our next-gen GLP-1 pipeline landscape.

What did the Phase 2 trial show?

In the Phase 2 trial, MariTide cut body weight by up to about 20% at 52 weeks in people with obesity and no diabetes, and up to about 17% in people with obesity and type 2 diabetes. Weight loss had not plateaued by the end of the trial.

The Phase 2 study was randomized, double-blind, and placebo-controlled. Final results were presented at the American Diabetes Association's 85th Scientific Sessions in June 2025 and published the same day (NEJM, 2025).

The trial split people into two groups. One had obesity without diabetes (n=465). The other had obesity plus type 2 diabetes (n=127) (Amgen, 2025).

In the no-diabetes group, MariTide produced mean weight loss of 16.3% to 19.9% across the higher dose arms, against 2.5% to 2.6% for placebo (Amgen, 2025).

In the diabetes group, weight loss ran 12.1% to 17.0%, against 1.4% to 1.7% for placebo (Amgen, 2025).

Blood sugar improved too. In the diabetes group, MariTide lowered A1C by up to 2.2 percentage points (NEJM, 2025).

The no-plateau finding matters most. Because the weight curve was still falling at 52 weeks, the real ceiling is likely higher than 20%, which is part of why Phase 3 runs to 72 weeks (Amgen, 2025).

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Here is the evidence laid out by trial, population, and dose. Full data appears in the trial table.

Trial / arm (year)	Population	Dose / schedule	Sample (n)	Weight change
Phase 1, highest dose (2024)	Obesity, no T2D	Monthly SC	~110 total	-14.5% at day 85
Phase 1, placebo (2024)	Obesity, no T2D	Monthly SC	~110 total	-1.5% at day 85
Phase 2, higher arms (2025)	Obesity, no T2D	Monthly SC	465	-16.3% to -19.9% at 52 wk
Phase 2, placebo (2025)	Obesity, no T2D	Monthly SC	465	-2.5% to -2.6% at 52 wk
Phase 2, higher arms (2025)	Obesity + T2D	Monthly SC	127	-12.1% to -17.0% at 52 wk
Phase 2, placebo (2025)	Obesity + T2D	Monthly SC	127	-1.4% to -1.7% at 52 wk
MARITIME-1 Phase 3 (ongoing)	Obesity, no T2D	Monthly SC, 3 doses	~3,500	Reads out early 2027

Note that the Phase 2 numbers use the efficacy estimand, which measures the effect while people stay on the drug. The treatment-policy estimand, which counts everyone regardless of dropout, was lower, at roughly 12% to 16% in the no-diabetes group (Amgen, 2025).

Why is monthly dosing a big deal?

Every other major obesity drug is a weekly shot, so a once-monthly option means roughly 12 injections a year instead of 52. Fewer shots can mean better adherence, and adherence is the weak point of long-term weight care.

Most people who start a GLP-1 drug stop within a year or two. Weekly injections, cost, and side effects all play a part. Cutting the shot count by more than four-fold removes one of those barriers.

The clinical logic is simple. A drug only works if people keep taking it, and a monthly rhythm is easier to stick to than a weekly one (Amgen, 2025).

Monthly dosing is possible because of the antibody backbone. The molecule's long half-life keeps drug levels steady between doses, so a once-a-month shot still covers the full month (Nature Metabolism, 2024).

There is even talk of less-frequent options. Amgen has described MariTide as suitable for "monthly or less frequent" dosing, which could open the door to maintenance schedules spaced further apart (Amgen, 2025).

What happened to weight after stopping MariTide?

In the Phase 1 trial, people kept their weight loss for up to 150 days after their last dose, with peak weight loss holding for about two months off the drug. That durability is MariTide's standout differentiator.

Weight regain is the Achilles' heel of obesity drugs. After people stop semaglutide or tirzepatide, much of the lost weight tends to come back within a year, because the drug clears the body fast.

MariTide behaves differently. In the Phase 1 study, the highest dose drove 14.5% weight loss by day 85, versus 1.5% for placebo (Inside Precision Medicine, 2024).

Then came the surprise. After the last dose, weight loss was maintained for up to 150 days, and the maximum weight loss held for roughly two months off the drug (PharmExec, 2024).

Why does it linger? The same long half-life that allows monthly dosing also means the drug fades slowly after the last shot, so the effect tapers instead of snapping back (Nature Metabolism, 2024).

A fair caveat. This durability signal comes from the small Phase 1 trial. The Phase 2 study added a second part to test weight maintenance and durability after stopping, and those results were still maturing in 2026 (Amgen, 2025).

If the signal holds in larger trials, it could change how doctors think about maintenance. A drug that keeps weight off between sparse doses would be a real shift from the weekly drugs we have now.

How does MariTide compare to semaglutide, tirzepatide, and retatrutide?

MariTide's headline weight loss of about 20% sits between tirzepatide and retatrutide, but it is the only one dosed monthly and the only one that blocks GIP. The numbers below come from separate trials, so treat them as a rough lineup, not a head-to-head.

Semaglutide produces around 15% weight loss in its pivotal obesity trial. Tirzepatide reaches roughly 21% to 23%. Retatrutide, still investigational, has hit 24% in Phase 2 and 28% in Phase 3 (Lilly TRIUMPH-1, 2026).

MariTide's ~20% lands in the same neighborhood as tirzepatide on raw weight loss. The difference is the package: one monthly shot, GIP blockade, and a durability signal after stopping (NEJM, 2025).

Here is the side-by-side lineup across mechanism and dosing.

Drug	Mechanism	Dosing	Peak weight loss (trial)
Semaglutide	GLP-1 agonist	Weekly	~15%
Tirzepatide	GIP + GLP-1 agonist	Weekly	~21-23%
Retatrutide	GIP + GLP-1 + glucagon agonist	Weekly	~24% (Ph2), ~28% (Ph3)
MariTide	GIP antagonist + GLP-1 agonist	Monthly	~20% (Ph2)

One honest limit. No published trial has put MariTide directly against any of these drugs, so cross-trial comparisons can mislead. Different patients, different lengths, different measures.

For a deeper compare of the late-stage contenders, see our CagriSema vs tirzepatide vs retatrutide breakdown. The GIP-blocking angle also connects to a broader debate covered in our look at GIP-only agonists and the next mechanistic wave.

What are the side effects and FDA status?

The most common side effects are gastrointestinal, mainly nausea and vomiting, and MariTide is not FDA-approved; its Phase 3 MARITIME program reads out starting in early 2027. The GI profile, especially vomiting, drove changes to the Phase 3 dosing plan.

In Phase 2, GI events were the most common side effects and were mostly mild to moderate (NEJM, 2025).

Vomiting stood out. In one Phase 1 dosing scheme, vomiting affected roughly 22% to 24% of people, higher than the rates usually seen with weekly drugs (Amgen, 2025).

The fix was slower dose escalation. Starting low and stepping up cut both the GI events and the dropout rate, with discontinuation for side effects falling to about 7.8% or lower (Amgen, 2025).

That lesson shaped Phase 3. The MARITIME program titrates the dose up over weeks, starting around 21 mg before climbing, to keep nausea in check (Amgen, 2025).

Now the status. MariTide is investigational and not approved by the FDA for any use as of 2026 (NEJM, 2025).

The Phase 3 MARITIME program is large. MARITIME-1, the main obesity trial, plans to enroll about 3,500 adults without diabetes and measures weight change at 72 weeks (ClinicalTrials.gov NCT06858839).

The timing is the key fact. MARITIME-1 has a primary readout slated for early 2027, with extra trials in diabetes, cardiovascular disease, heart failure, and sleep apnea (ClinicalTrials.gov NCT06858839).

A standard FDA review after that would push the earliest realistic approval to late 2027 or 2028. Until then, MariTide stays a trial drug, not a prescription.

The bottom line

MariTide is the most distinct obesity drug in late-stage trials. It blocks GIP instead of activating it, it is dosed monthly instead of weekly, and early data hint that weight loss may stick after stopping.

The weight loss itself, about 20% in Phase 2, is strong but not record-setting next to retatrutide. The real story is convenience and durability. A monthly shot that holds weight off between doses would solve the adherence problem that limits today's drugs.

The open questions are real. The durability signal is from a small Phase 1 trial, the vomiting rate needs taming, and the big Phase 3 data will not arrive until early 2027 (NEJM, 2025). For now, MariTide is one of the most-watched names in obesity, but it is not approved and not available.

Related Reading

• Retatrutide: complete evidence review
• Next-gen GLP-1 pipeline: the 2026 landscape
• GIP-only agonists: the next mechanistic wave

Frequently asked questions

Is MariTide FDA-approved in 2026?

No. As of 2026, MariTide (maridebart cafraglutide, AMG 133) is investigational and not approved by the FDA for any use. Its Phase 3 MARITIME-1 obesity trial has a primary readout slated for early 2027, which means the earliest realistic approval would be late 2027 or 2028.

How much weight do people lose on MariTide?

In the Phase 2 trial, MariTide produced mean weight loss of up to about 20% at 52 weeks in people with obesity and no diabetes, and up to about 17% in people with obesity and type 2 diabetes. Weight loss had not plateaued at 52 weeks, suggesting the ceiling may be higher.

How is MariTide different from tirzepatide?

Tirzepatide activates both the GIP and GLP-1 receptors and is dosed weekly. MariTide activates GLP-1 but blocks the GIP receptor, and it is dosed monthly. Despite the opposite GIP approach, both drugs deliver roughly 20% weight loss in trials.

Does weight come back after stopping MariTide?

In the small Phase 1 trial, weight loss was maintained for up to 150 days after the last dose, with peak weight loss holding for about two months off the drug. This durability is tied to MariTide's long half-life, but it still needs confirmation in larger Phase 2 and Phase 3 trials.

What are the most common MariTide side effects?

Gastrointestinal symptoms are most common, mainly nausea and vomiting, and they were mostly mild to moderate. Vomiting was notable in early dosing schemes, affecting roughly 22% to 24% of people, which led Amgen to use slower dose escalation in Phase 3 to improve tolerability.

-- The GLP-1 Daily Team