MariTide (maridebart cafraglutide) is a once-monthly injectable weight-loss therapy combining GIP receptor blockade and GLP-1 agonism. In recent trials (phase 2), it achieved average weight loss of 16%–20% at 52 weeks—more than Wegovy (~15%) and approaching Zepbound (~21%)—with potential convenience advantages for patients, but higher gastrointestinal side effects at top doses.

How Do MariTide, Wegovy, and Zepbound Work for Weight Loss?

While all three target hormones involved in appetite and metabolism, each uses a distinct strategy to promote weight loss. Here’s a quick overview of the mechanisms behind MariTide, Wegovy, and Zepbound.

MariTide (maridebart cafraglutide):

• Dual action: GLP-1 (glucagon-like peptide-1) receptor agonist (stimulates GLP-1 pathway, reducing appetite and food intake) plus GIP (glucose-dependent insulinotropic polypeptide) receptor antagonist (blocks GIP, a hormone involved in insulin and fat regulation).
• Unique structure: Antibody-peptide conjugate with a long half-life, enabling monthly dosing.

Wegovy (semaglutide):

• Mechanism: Pure GLP-1 receptor agonist. Mimics natural GLP-1 to suppress appetite, slow gastric emptying, and promote insulin release.

Zepbound (tirzepatide):

• Mechanism: Dual GIP and GLP-1 receptor agonist. Activates both pathways to enhance weight loss and metabolic effects.

While it can be confusing that MariTide and Zepbound have opposing actions regarding the GIP pathway (MariTide blocks it, while Zepbound activates it), there is evidence supporting both mechanisms for weight loss. One theory is that activating this pathway reduces GIP receptors and activity overall after some time, which has the same effect as blocking it. More research is needed to fully understand the effects of activating and blocking the GIP pathway on weight loss.

Head-to-Head Efficacy

There are currently no head-to-head clinical trials comparing MariTide, Wegovy, and Zepbound, but we can compare data from multiple studies.

Drug and Dose	Mean % Weight Loss	Duration	Frequency	Study
MariTide 420 mg	16–20%	52 weeks	Once monthly	NEJM 2025 (phase 2 clinical trials)
Semaglutide (Wegovy) 2.4 mg	15%	68 weeks	Once weekly	STEP 1
Tirzepatide (Zepbound) 15 mg	21%	72 weeks	Once weekly	SURMOUNT-1

MariTide lands between Wegovy and Zepbound on weight loss, but wins on dosing burden as it is a once-monthly (or less frequently) injection.

Dose and Administration

All three medications are dosed as an under-the-skin injection, but the frequency differs. Wegovy and Zepbound come as prefilled pens that are administered once a week, while MariTide is injected once a month via an autoinjector device. Studies are exploring even less frequent dosing of MariTide.

Side Effect Profiles

Gastrointestinal symptoms are common with GLP-1 and GIP therapies, but the frequency and severity can vary between MariTide, Wegovy, and Zepbound. Here’s how their side effect profiles compare.

Side Effect	MariTide (420 mg, monthly)*	Wegovy (2.4 mg, weekly)	Zepbound (15 mg, weekly)
Nausea	22-69%	44%	28%
Vomiting	36-69%	24%	13%
Diarrhea	7-17%	30%	23%
Constipation	11-19%	24%	11%
Abdominal pain	-	20%	10%
Discontinuation due to side effects	8–27% (lower with dose escalation)	~7%	~7%

*Range includes patients taking 420 mg weekly without dose escalation, with a 4-week dose escalation, and 12-week dose escalation.

Other common side effects (fatigue and injection site reactions) occur across all three medications but at lower frequencies. Serious but rare risks (pancreatitis, gallbladder disease, allergic reactions) are highlighted in prescribing information for Wegovy and Zebound.

Related questions

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Cardiometabolic Effects

All three medications have been shown in studies to lower HbA1c (a blood test that shows average blood glucose levels over 3 months), blood pressure, and triglycerides. In people with type 2 diabetes, HbA1c dropped by about 1.5% with MariTide, with many achieving normal blood sugar after a year. This is compared to a reduction of up to 2.1% in patients taking 15 mg of Zepbound, and up to 1.6% in patients taking Wegovy.

Studies are ongoing to look at the effects of MariTide in people with heart failure as well as those with a cardiovascular condition.

Convenience and Adherence

Convenience plays a major role in long-term adherence to weight-loss medications. MariTide’s once-monthly injection sets it apart from Wegovy and Zepbound, which require weekly dosing. Fewer injections may make it easier for patients to stick with treatment.

As studies continue, monthly dosing could prove to be a significant advantage for those seeking a simpler routine. Additional studies are ongoing to look at even less frequent dosing, such as every 8 weeks. The MARITIME Phase-3 program aims to confirm the once-monthly benefit.

Cost and Coverage Outlook

The cost and insurance coverage of weight-loss medications are major factors influencing patient access and long-term use. While list prices for Wegovy and Zepbound have historically been over $1,000 per month, recent price cuts and new direct-to-patient programs are making these treatments more affordable—especially for those without insurance or with limited coverage.

Coverage and out-of-pocket costs can still vary widely depending on insurance plans and available discount programs. MariTide’s pricing is yet to be announced, with details expected closer to its anticipated launch. Prices below are based on Drugs.com Price Guide using a free Drugs.com discount card. These prices are subject to change based on location and pharmacy.

• Wegovy: $1,349 for a 1-month supply
• Zepbound: $1,169 for a 1-month supply

Regulatory Timelines

• MariTide: Phase 3 results expected in 2027, with FDA submission planned the same year.
• Wegovy: FDA approved in 2021.
• Zepbound: FDA approved in 2023.

Who Might Choose Which?

When choosing a weight loss medication, there are several factors to consider. Side effects, dosing, and efficacy are a few points to evaluate before making a decision with your healthcare provider.

• MariTide: Best for patients seeking fewer injections and willing to manage early-phase GI symptoms.
• Wegovy: Preferred for those wanting the longest safety record and a GLP-1–only mechanism.
• Zepbound: Offers the highest published weight loss, but requires weekly dosing and is priced similarly to other injectable weight loss drugs.

What About Ozempic?

Ozempic is the lower-dose, type 2 diabetes version of semaglutide. It is often prescribed off-label for weight loss, but achieves only about 6% weight loss at approved doses (0.5–1 mg weekly)—about half that of Wegovy and below MariTide’s mid-dose results. It shares Wegovy’s weekly injection schedule.

This is not all the information you need to know about Wegovy, Zepbound, Ozempic, or MariTide for safe and effective use and does not take the place of your doctor’s directions. Review the full patient medication guide and discuss this information and any questions you have with your doctor or other health care provider.

References

1. Amgen. (2024, November 26). AMGEN ANNOUNCES ROBUST WEIGHT LOSS WITH MARITIDE IN PEOPLE LIVING WITH OBESITY OR OVERWEIGHT AT 52 WEEKS IN A PHASE 2 STUDY. Amgen. https://www.amgen.com/newsroom/press-releases/2024/11/amgen-announces-robust-weight-loss-with-maritide-in-people-living-with-obesity-or-overweight-at-52-weeks-in-a-phase-2-study
2. Amgen. (2025, June 26). A Phase 3 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Maridebart Cafraglutide in Adult Participants With Type 2 Diabetes Mellitus Who Have Obesity or Are Overweight (MARITIME-2). ClinicalTrials.gov. Accessed on June 29, 2025 at https://www.clinicaltrials.gov/study/NCT06858878?intr=maridebart%20cafraglutide&rank=6
3. Campbell J. E. (2021). Targeting the GIPR for obesity: To agonize or antagonize? Potential mechanisms. Molecular metabolism, 46, 101139. https://doi.org/10.1016/j.molmet.2020.101139
4. de Lemos, J. A., Linetzky, B., le Roux, C. W., Laffin, L. J., Vongpatanasin, W., Fan, L., Hemmingway, A., Ahmad, N. N., Bunck, M. C., & Stefanski, A. (2024). Tirzepatide Reduces 24-Hour Ambulatory Blood Pressure in Adults With Body Mass Index ≥27 kg/m2: SURMOUNT-1 Ambulatory Blood Pressure Monitoring Substudy. Hypertension, 81(4), e41–e43. https://doi.org/10.1161/HYPERTENSIONAHA.123.22022
5. Drugs.com. (2025, January 21). How much weight can I lose on Zepbound? Accessed on June 29, 2025 at https://www.drugs.com/medical-answers/how-weight-lose-zepbound-3575539/
6. Drugs.com. (2025, January 30). How do Ozempic, Mounjaro, Wegovy, Zepbound compare for weight loss? Accessed on June 29, 2025 at https://www.drugs.com/medical-answers/mounjaro-wegovy-ozempic-compare-weight-loss-3570898/
7. Fierce Biotech. 2025. Amgen rolls out phase 3 dosing plan for lead obesity candidate after midstage trial sees high discontinuation, vomiting rates. Accessed on June 29, 2025 at https://www.fiercebiotech.com/biotech/amgen-adjusts-phase-3-dosing-plan-lead-obesity-candidate-maritide-after-high
8. Jastreboff, A. M., Ryan, D. H., Bays, H. E., Ebeling, P. R., Mackowski, M. G., Philipose, N., Ross, L., Liu, Y., Burns, C. E., Abbasi, S. A., Pannacciulli, N., & MariTide Phase 2 Obesity Trial Investigators (2025). Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity - A Phase 2 Trial. The New England journal of medicine, 10.1056/NEJMoa2504214. Advance online publication. https://doi.org/10.1056/NEJMoa2504214
9. Jastreboff, A. M., Aronne, L. J., Ahmad, N. N., Wharton, S., Connery, L., Alves, B., Kiyosue, A., Zhang, S., Liu, B., Bunck, M. C., Stefanski, A., & SURMOUNT-1 Investigators (2022). Tirzepatide Once Weekly for the Treatment of Obesity. The New England journal of medicine, 387(3), 205–216. https://doi.org/10.1056/NEJMoa2206038
10. Javor, E., Lucijanić, M., & Skelin, M. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. The New England journal of medicine, 385(1), e4. https://doi.org/10.1056/NEJMc2106918
11. Kennedy, C., Hayes, P., Salama, S., Hennessy, M., & Fogacci, F. (2023). The Effect of Semaglutide on Blood Pressure in Patients without Diabetes: A Systematic Review and Meta-Analysis. Journal of clinical medicine, 12(3), 772. https://doi.org/10.3390/jcm12030772
12. MariTime. About the MARITIME-1 study. Accessed on June 29, 2025 at https://www.maritimestudy.com/en-us/maritime-1
13. Novo Nordisk. (2023). Ozempic® and Weight. NovoMedLink. https://www.novomedlink.com/diabetes/products/treatments/ozempic/efficacy-safety/ozempic-and-weight.html
14. Ozempic [package insert]. Updated January 2025. Novo Nordisk. Accessed on June 30, 2025 at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=adec4fd2-6858-4c99-91d4-531f5f2a2d79
15. Ozempic.com. Accessed June 30, 2025 at https://www.ozempic.com/why-ozempic/diabetes-medicines-comparison.html#weightInfo
16. Véniant, M. M., Lu, S. C., Atangan, L., Komorowski, R., Stanislaus, S., Cheng, Y., Wu, B., Falsey, J. R., Hager, T., Thomas, V. A., Ambhaikar, M., Sharpsten, L., Zhu, Y., Kurra, V., Jeswani, R., Oberoi, R. K., Parnes, J. R., Honarpour, N., Neutel, J., & Strande, J. L. (2024). A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings. Nature metabolism, 6(2), 290–303. https://doi.org/10.1038/s42255-023-00966-w
17. Wegovy [package insert]. Updated November 2024. Novo Nordisk. Accessed on June 30, 2025 at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b
18. Zepbound [package insert]. Updated May 2025. Eli Lilly and Company. Accessed on June 30, 2025 at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b

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