How the New Once‑Monthly Weight‑Loss Injection (MariTide) Compares to Wegovy and Zepbound
Daniel Zvi
Introduction: The explosion of GLP‑1 weight‑loss drugs
In the past few years, injections originally designed to treat diabetes have revolutionised the weight‑loss market. Brand‑name drugs such as Wegovy (semaglutide) and Zepbound (tirzepatide) work by mimicking gut hormones that curb appetite and slow digestion. They are administered once a week and deliver double‑digit weight loss in many users. However, these medicines require strict adherence to weekly injections, and shortages have made access difficult. Amgen’s investigational drug MariTide (also known as maridebart cafraglutide) aims to disrupt that landscape by extending the interval between doses to a month.
What is MariTide?
MariTide is a glucagon‑like peptide‑1 (GLP‑1) receptor agonist developed by Amgen. Like Wegovy, it mimics the GLP‑1 hormone to suppress appetite, slow stomach emptying and stimulate insulin production. MariTide also contains an engineered antibody that blocks the glucose‑dependent insulinotropic polypeptide (GIP) receptor, a novel twist because tirzepatide activates the GIP receptor. Early studies suggest that both activation and inhibition of the GIP pathway can aid weight loss, but the combination of a peptide and a monoclonal antibody means the drug stays in the bloodstream for 21 days. As a result, MariTide can be given once a month (or even every three weeks), whereas Wegovy and Zepbound require weekly injections.
Phase‑2 trial results
The largest evidence so far comes from a 52‑week phase 2 trial involving 592 participants with obesity, 127 of whom also had type 2 diabetes. Participants were randomised to receive one of three monthly doses (140 mg, 280 mg or 420 mg) or a placebo. Results were impressive:
- People with obesity but without diabetes lost 16.2 % of their body weight on average; when excluding dropouts the loss reached 19.9 %.
- Participants with obesity and diabetes lost 12.3 % on average, or 17 % when excluding dropouts.
- Weight‑loss curves did not plateau at 52 weeks, suggesting continued loss is possible.
- The trial noted improvements in blood pressure, inflammatory markers, lipid levels and a 2.2 percentage‑point reduction in HbA1c.
These results place MariTide between semaglutide and tirzepatide in terms of efficacy. Importantly, the phase‑2 study indicates that the monthly shot could achieve high weight loss without weekly injections. Phase‑3 “MARITIME” trials will determine whether these benefits persist in larger, diverse populations.
(Jastreboff et al., 2025, New England Journal of Medicine).
How does it work?
MariTide’s design combines a GLP‑1 receptor agonist with a GIP receptor antagonist and a monoclonal antibody. The GLP‑1 agonist curbs hunger and improves insulin secretion. The GIP antagonist blocks one of the incretin hormones that normally stimulates insulin; paradoxically, inhibiting this pathway may enhance satiety and fat burning. The monoclonal antibody prolongs the drug’s half‑life so that it remains active for roughly 21 days. This long half‑life is what allows once‑monthly dosing.
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Medical Evaluation
Comparison with Wegovy (semaglutide) and Zepbound (tirzepatide)
Mechanism and dosing
| Drug | Mechanism | Dosing frequency | Key differentiator |
| MariTide (maridebart cafraglutide) | GLP‑1 receptor agonist + GIP receptor antagonist with an antibody that extends its half‑life | Monthly | Novel peptide–antibody conjugate allows 21‑day half‑life; early trials only |
| Wegovy (semaglutide) | GLP‑1 receptor agonist that suppresses appetite and slows gastric emptying | Weekly | FDA‑approved; average weight‑loss of about 15 % over 68 weeks |
| Zepbound (tirzepatide) | Dual GLP‑1 and GIP receptor agonist | Weekly | FDA‑approved; produced about 21 % weight‑loss over 72 weeks in trials |
While Wegovy and Zepbound rely solely on weekly peptide injections, MariTide adds a monoclonal antibody to the mix. This structural difference makes MariTide the first once‑monthly GLP‑1 weight‑loss injection on the horizon.
Efficacy and weight‑loss outcomes
Clinical data show that MariTide’s efficacy sits between that of semaglutide and tirzepatide. In the phase‑2 trial, MariTide led to 12 %–16 % average weight loss (intent‑to‑treat) and up to 20 % when excluding dropouts after 52 weeks. By comparison, semaglutide users lost about 15 % of body weight over 68 weeks, while tirzepatide users lost about 21 % over 72 weeks. Importantly, weight loss on MariTide had not plateaued at one year, so the final efficacy could approach that of Zepbound.
Side effects and tolerability
Like other GLP‑1–based drugs, MariTide’s most common side effects were gastrointestinal – nausea, vomiting, constipation, dry heaving and diarrhoea. These symptoms were typically mild to moderate and often occurred during dose escalation. Starting at lower doses and gradually increasing improved tolerability. Semaglutide and tirzepatide share similar GI side effects; however, tirzepatide also carries FDA warnings about potential thyroid tumours and requires close monitoring.
Cardiometabolic benefits
Besides weight reduction, GLP‑1 drugs offer metabolic advantages. In the MariTide trial, participants experienced improvements in blood pressure, cholesterol and inflammation markers, along with a 2.2‑point drop in HbA1c. Semaglutide and tirzepatide trials similarly reported better glucose control and lipid profiles, but head‑to‑head comparisons are lacking. Existing evidence suggests that tirzepatide may slightly outperform semaglutide in weight loss, but the studies used different doses and cannot be directly compared.
Availability and cost
Wegovy and Zepbound are FDA‑approved and available by prescription; both are expensive and often in short supply. Consumer‑grade pricing can exceed US$1,000 per month, and insurance coverage varies widely. MariTide is not yet approved; phase‑3 MARITIME trials will run through 2025–2026 and optimised dosing strategies must be confirmed. If approved, the once‑monthly schedule could improve adherence and reduce clinic visits. Its cost remains unknown, but Amgen may price it competitively to gain market share.
Is MariTide worth waiting for?
The data so far are promising: a monthly GLP‑1 injection that produces weight loss approaching Zepbound while offering the convenience of fewer shots and potentially better adherence. However, several caveats remain:
- Limited trial data: Phase‑2 results, though encouraging, are based on fewer than 600 participants, with a 28 % dropout rate. Phase‑3 studies will need to confirm efficacy and safety in larger, more diverse populations.
- Long‑term safety unknown: Gastrointestinal side effects were common but manageable. Rare adverse events, such as pancreatitis or gallbladder issues, may emerge when tested on thousands of people.
- Regulatory timeline: Even if phase‑3 results are positive, FDA approval may not occur until 2026 or later. Patients seeking immediate weight management may prefer Wegovy or Zepbound in the meantime.
Conclusion
MariTide represents a significant innovation in obesity pharmacotherapy. By combining a GLP‑1 agonist with a GIP antagonist and a monoclonal antibody, Amgen has engineered a once‑monthly injection that achieved up to 20 % weight loss in phase‑2 trials. Its efficacy appears to fall between Wegovy’s 15 % and Zepbound’s 21 % weight loss while offering the convenience of fewer injections. If upcoming phase‑3 trials confirm these findings and the drug receives FDA approval, MariTide could be a game‑changer for people seeking sustained weight loss without weekly injections. Until then, consumers and clinicians should continue to rely on existing approved therapies and monitor the progress of this promising new drug.
Frequently Asked Questions
Q. What is MariTide?
A. MariTide is an investigational weight-loss drug developed by Amgen. It combines a GLP‑1 receptor agonist with a GIP receptor antagonist, attached to a monoclonal antibody. This structure allows it to be taken just once a month, instead of weekly like Wegovy or Zepbound.
Source: Jastreboff et al., NEJM, 2025
Q. How does MariTide work?
A. It activates the GLP‑1 receptor to suppress appetite and regulate insulin, while blocking the GIP receptor—a novel approach that may enhance satiety and fat burning. The monoclonal antibody extends the drug’s half-life to about 21 days, enabling monthly injections.
Source: NEJM Supplementary Protocol, 2025
Q. How effective is it for weight loss?
A. In a 52-week phase 2 trial:
- People without diabetes lost an average of 16.2% of their body weight, or 19.9% excluding dropouts.
- People with type 2 diabetes lost 12.3% on average, or 17% excluding dropouts.
Weight-loss curves did not plateau at 52 weeks, suggesting continued potential.
Q. How does MariTide compare to Wegovy and Zepbound?
A.
- MariTide: Monthly injection, ~16–20% weight loss in early trials
- Wegovy (semaglutide): Weekly, ~15% over 68 weeks
- Zepbound (tirzepatide): Weekly, ~21% over 72 weeks
MariTide offers fewer injections with competitive weight loss, but it’s still in trials.
Q. What side effects were reported?
A. The most common side effects were nausea, vomiting, diarrhea, constipation, and dry heaving. These were generally mild to moderate and most frequent during the dose escalation phase.
Q. Does it offer other health benefits?
A. Yes. The trial demonstrated improvements in blood pressure, cholesterol levels, and inflammatory markers, as well as a 2.2-point decrease in HbA1c in individuals with type 2 diabetes.
Q. Is MariTide FDA-approved?
A. No. It is still in clinical trials. Phase 3 studies are underway as part of Amgen’s MARITIME program.
Q. When will it be available?
A. If phase 3 results are positive and regulators approve the drug, it could become available in 2026 or later.
Q. Why does MariTide block GIP instead of activating it like Zepbound?
A. Unlike Zepbound, which activates GIP, MariTide blocks it. Some genetic and preclinical studies suggest GIP inhibition may aid weight loss. This alternative mechanism may also improve fat metabolism.
Source: ADA Meeting News, 2025
Q. What happens if you stop taking MariTide?
A. That’s not yet known. The phase 2 trial didn’t study discontinuation effects. A follow-up trial is examining weight maintenance, reduction, or rebound after stopping or lowering doses.
Q. How much will it cost?
A. Pricing hasn’t been announced. Comparable drugs like Wegovy and Zepbound retail for over $1,000/month without insurance. Amgen may price MariTide competitively, but that’s speculative for now.
Q. Should I wait for MariTide or use available treatments now?
A. If you’re interested in a monthly option and can wait, MariTide is promising. But if you need treatment now, Wegovy and Zepbound are FDA-approved and effective. Talk to a doctor about what’s best for your goals.
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