What Is MariTide?

1. How does MariTide work?

Maridebart cafraglutide is two drugs in one molecule. The scaffold is a monoclonal antibody that binds and blocks the GIP receptor. Attached to it are two copies of a GLP-1 analogue peptide that activate the GLP-1 receptor, the same target as semaglutide. Because antibodies circulate for weeks, the whole conjugate does too, which is what allows dosing every 4 or 8 weeks instead of weekly.

The GIP half is the unusual part. Tirzepatide activates the GIP receptor; MariTide blocks it. Both produce large weight loss in trials, and that paradox is unresolved. One reading is that chronic GIP agonism desensitises the receptor and ends up functionally similar to blocking it; another is that GIP matters less than the GLP-1 component either way. The what is GIP page lays out the evidence on both sides.

The molecule’s earlier development, published in Nature Metabolism, confirmed GIPR antagonist and GLP-1R agonist activity in cell-based assays, then showed weight loss and improved metabolic markers in obese mice and cynomolgus monkeys. The first human data came from a Phase 1 randomised, double-blind, placebo-controlled study, NCT04478708, which reported an acceptable safety and tolerability profile with pronounced dose-dependent weight loss; in the multiple-ascending-dose cohorts, weight loss was maintained for up to 150 days after the last dose, evidence for the long duration of action that supports monthly or less-frequent dosing.

2. How much weight do people lose on MariTide?

The Phase 2 trial, NCT05669599, randomised 592 adults to maridebart cafraglutide or placebo for 52 weeks: 465 with obesity or overweight and no diabetes, and 127 with obesity and type 2 diabetes. Doses were 140, 280, or 420 mg every 4 weeks, some arms with escalation from a lower start, plus one arm at 420 mg every 8 weeks. The registry record shows a two-part design: Part 1 randomised 7 dose cohorts in the non-diabetes group and 4 dose cohorts in the diabetes group; Part 2 re-randomised both groups into 4 further dose cohorts to refine the dose-escalation schedule ahead of Phase 3. Secondary endpoints also reported improvements in waist circumference, blood pressure, high-sensitivity C-reactive protein, and lipid parameters, alongside the weight and HbA1c results.

Eligibility followed the pattern of other obesity trials: a BMI of 30 kg/m² or higher, or 27 kg/m² or higher with a weight-related comorbidity, plus a history of unsuccessful weight-loss attempts; the diabetes cohort additionally required an HbA1c of 7% to 10% with type 2 diabetes diagnosed at least 180 days earlier. People with a history of pancreatitis, medullary thyroid carcinoma or MEN2, or recent major psychiatric illness were excluded.

Two estimands are reported, and the difference explains the two sets of numbers in circulation. The NEJM treatment-policy estimand counts every participant regardless of whether they stopped the drug, and gives 12.3% to 16.2% without diabetes and 8.4% to 12.3% with diabetes. Amgen’s efficacy estimand counts people while on treatment, and gives up to about 20% against 2.6% without diabetes and about 17% against 1.4% with diabetes. Both are real; the first is the conservative one.

For scale, in separate trials with different populations, semaglutide 2.4 mg produced 14.9% at 68 weeks (STEP 1) and tirzepatide 15 mg 20.9% at 72 weeks (SURMOUNT-1). MariTide’s 52-week treatment-policy numbers sit between them; its efficacy-estimand numbers sit at the top. None of these are head-to-head.

3. What are the side effects of MariTide?

Gastrointestinal, as with every incretin drug, and the trial’s design question was how to manage them at a monthly dose. The NEJM paper reports that gastrointestinal adverse events were common, mainly nausea and vomiting, and were less frequent in the arms that started at a lower dose and escalated than in the arms that started at the full dose. Amgen reports discontinuation because of gastrointestinal events of up to 7.8% in the escalation arms, lower than in the non-escalation arms. No unexpected safety signals emerged.

The practical consequence is that Phase 3 uses dose escalation from the start. The lesson from Phase 2 was that a monthly drug cannot be started at its full dose.

That lesson dates back further, to a separate Phase 1 study Amgen calls the PK-LDI study (pharmacokinetics and low-dose initiation), which tested whether starting at a smaller dose before stepping up would reduce vomiting. A 21/70/350 mg escalation schedule produced vomiting in 24.4% of participants and a 35/70/350 mg schedule in 22.5%, with no discontinuations for gastrointestinal events in that study. Phase 2 built on that groundwork by comparing full-dose starts against escalation directly, in a larger population, over a full year.

4. What is the MARITIME program?

Three Phase 3 trials, all randomised, double-blind, and placebo-controlled. MARITIME-1 and MARITIME-2 have a 72-week primary endpoint of percent weight change. MARITIME-CV’s primary endpoints are time to first occurrence of major adverse cardiovascular events, over an estimated 35 months: a three-point composite of cardiovascular death, myocardial infarction, or ischemic stroke, and a five-point composite that adds all-cause death, coronary revascularization, and heart failure events.

MARITIME-1 and MARITIME-2 are the registrational trials. MARITIME-CV is the cardiovascular outcomes trial, the kind that gave Wegovy its heart indication in SELECT. No regulatory filing has been announced, and the earliest realistic path is a filing after the 2027 readouts.

Beyond obesity and diabetes, Amgen has registered four more Phase 3 or Phase 2 trials of maridebart cafraglutide: NCT07037459 in heart failure with preserved or mildly reduced ejection fraction plus obesity, NCT07226765 in obstructive sleep apnea for people not on PAP therapy, NCT07225686 in obstructive sleep apnea for people on PAP therapy, and NCT07441252, a Phase 2 trial in adults with elevated liver fat and obesity or overweight. All four were recruiting when checked.

The heart failure and sleep apnea trials follow a pattern set by other GLP-1 drugs’ outcome trials, though not by their approved labels. Semaglutide’s own STEP-HFpEF trial showed benefit in heart failure with preserved ejection fraction, but Wegovy’s FDA label lists cardiovascular risk reduction and weight reduction, not an HFpEF indication. Obstructive sleep apnea is an approved indication for tirzepatide, as Zepbound, not for semaglutide. Lilly’s SUMMIT trial tested tirzepatide in HFpEF; that too is a trial result, not an approved indication. Amgen is testing whether weight loss from a GIP-antagonist mechanism produces similar benefits in both conditions. The liver fat trial is earlier stage, Phase 2.

5. How does MariTide compare with the approved drugs?

The retatrutide page covers Lilly’s triple agonist, the other late-stage molecule aiming above tirzepatide. For a log, an investigational drug is entered like any other: product, date, milligrams, and site, with the dosing interval set to 4 or 8 weeks. How GLP-1 tracking works covers what to record.

6. MariTide FAQ

• How much weight do people lose on MariTide?

  In the Phase 2 trial published in NEJM, adults with obesity and no diabetes lost 12.3% to 16.2% of body weight at 52 weeks across the dose groups, against 2.5% on placebo, under the treatment-policy estimand that counts everyone regardless of whether they stopped. Adults with type 2 diabetes lost 8.4% to 12.3% against 1.7%. Amgen's efficacy estimand, which counts people while on treatment, reports up to about 20% and 17%.

• How often is MariTide injected?

  Once every 4 weeks in most Phase 2 arms, with one arm dosed every 8 weeks in the first year (Part 1). Amgen has since reported that in Part 2's second year, participants who had lost at least 15% of their body weight maintained it on a lower monthly dose or a quarterly (every-12-week) dose. The antibody scaffold gives the molecule a half-life long enough for infrequent dosing. Every approved GLP-1 injection is weekly or daily.

• How is MariTide different from tirzepatide?

  Both act on the GLP-1 and GIP receptors, in opposite directions at GIP. Tirzepatide activates the GIP receptor; MariTide blocks it. Both produce large weight loss, which is one reason the role of GIP in appetite is still debated. MariTide is also a monthly injection built on an antibody, where tirzepatide is a weekly peptide.

• What are the side effects of MariTide?

  Gastrointestinal events were the most common in Phase 2, mainly nausea and vomiting, and the NEJM paper reports they were less frequent with a lower starting dose and dose escalation. Discontinuation because of gastrointestinal events was up to 7.8% in the dose-escalation arms and higher in arms that started at the full dose. No unexpected safety signals were reported.

• Is MariTide being studied for anything besides obesity?

  Yes. Beyond the obesity and type 2 diabetes trials, Amgen has registered a Phase 3 trial in heart failure with preserved or mildly reduced ejection fraction (NCT07037459), two Phase 3 trials in obstructive sleep apnea, one for people on PAP therapy and one for people not on it (NCT07225686 and NCT07226765), and a Phase 2 trial in adults with elevated liver fat and obesity or overweight (NCT07441252). All were recruiting when last checked.

• Is MariTide FDA-approved?

  No. It is in Phase 3. MARITIME-1 and MARITIME-2 have finished enrolling with primary completion estimated for January 2027, and MARITIME-CV, a cardiovascular outcomes trial, is recruiting toward 12,800 participants with completion estimated in 2028. No filing has been announced.

7. Sources