MariTide – new drug treatment for obesity under development

Treatment of obesity

Obesity is a multifactorial and chronic condition influenced by a combination of biological, genetic, and environmental factors. Body weight is regulated by a complex interplay between the brain, hormones, and metabolism, where signals regarding hunger, satiety, and energy balance are constantly integrated. For a long time, obesity and overweight treatment has primarily focused on lifestyle changes. Although diet and physical activity are central parts of the treatment, it has become increasingly clear that biological mechanisms play a significant role. This has contributed to a shift in treatment perspectives where drug treatment is today seen as an important complement for many patients.

What is MariTide?

MariTide (maridebart cafraglutide, formerly AMG 133) is a drug under clinical development for the treatment of obesity and obesity-related conditions. It is being developed by the biotech company Amgen and is not yet approved for clinical use. What makes MariTide particularly interesting is its structure. It is a so-called peptide–antibody conjugate, which means it combines a peptide (which affects hormonal signals) with an antibody (which provides a long-lasting effect in the body). This construction enables a longer half-life compared to many existing treatments and opens the door for less frequent dosing, for example, monthly. The treatment is also being studied in several obesity-related conditions, reflecting a broader focus on the medical consequences of obesity, such as cardiovascular disease and sleep apnea.

How does MariTide work?

MariTide works by affecting central hormonal systems that regulate hunger, satiety, and energy balance:

 Activation of the GLP-1 receptor 

GLP-1 is a hormone released after a meal that signals satiety to the brain. Activation of the GLP-1 receptor leads to reduced appetite, increased feelings of fullness, and slower gastric emptying. By stimulating insulin release when blood sugar rises and inhibiting glucagon production, activation of the GLP-1 receptor contributes to more stable glucose levels. These are well-established mechanisms that also form the basis for drugs such as semaglutide. 

Blocking of the GIP receptor 

GIP is another hormone that affects metabolism, but its role in weight regulation is more complex and not yet fully mapped. MariTide blocks the GIP receptor, which represents a different strategy than previous drugs. Research suggests that this blockade, in combination with GLP-1 activation, can enhance the effect on energy balance and body weight. By combining these two effects, MariTide affects several parts of the body's regulation of energy intake and energy storage simultaneously.

How does MariTide differ from other weight loss drugs?

Current drug treatment for obesity is largely based on mimicking the body's own hormones. The most common treatments work in the following ways:

GLP-1 agonists (e.g., semaglutide/Wegovy)
Activate only the GLP-1 receptor and enhance the body's natural satiety signals. 

Dual agonists (e.g., tirzepatide/Zepbound)
Activate both the GLP-1 and GIP receptors, providing a combined hormonal effect. MariTide differs from these through its unique combination of:

• GLP-1 activation
• GIP blockade (instead of activation)

This means that MariTide represents a different biological strategy for affecting the same hormone system. While some drugs enhance GIP signaling, MariTide instead aims to dampen it. 

Another important difference is the drug's structure. Unlike current treatments, which are peptide-based and given as weekly injections, MariTide is an antibody-based conjugate with a longer half-life. This may enable less frequent dosing, which can be an advantage from both a treatment and compliance perspective.

What does the research show so far?

In clinical phase 2 studies, MariTide has shown clinically relevant and significant weight loss in people with obesity. The results suggest that the treatment can provide weight loss on par with the most effective drugs available today. The treatment has generally had a side-effect profile similar to that of GLP-1-based drugs, where gastrointestinal-related symptoms such as nausea, diarrhea, and vomiting are most common. However, it is important to emphasize that long-term data are still limited. Ongoing phase 3 studies will provide more information about the treatment's efficacy, safety, and tolerability over a longer time and in larger patient groups.

What role can MariTide play in the future?

It is still too early to determine exactly what place MariTide will have in the treatment of obesity. Treatment response varies between individuals, which means the effect may differ depending on biological and clinical conditions. For many patients, drug treatment is part of a broader treatment strategy. Long-term sustainable results are often achieved through a combination of medical treatment, dietary changes, physical activity, and support regarding behavior and mental health. If the ongoing phase 3 studies confirm the previous results, MariTide could become an important addition to today's treatment options. The longer duration of action can also contribute to simpler treatment schedules, which can potentially improve compliance.

What does this mean for the future?

MariTide is a clear example of how the treatment of obesity is developing toward more advanced and targeted drugs. By affecting several hormonal signaling pathways simultaneously, there is potential to further improve treatment outcomes. The development also reflects a larger change within obesity care. Today, there is an increased understanding that body weight is largely controlled by biological mechanisms, which has contributed to a shift from a sole lifestyle focus to more individualized and evidence-based treatment. In the future, more drugs with different mechanisms of action will likely be developed, which may enable more tailored treatment based on the individual's needs and conditions.

Summary

MariTide is an investigational drug under development that represents a new strategy for the treatment of obesity. By combining GLP-1 activation with GIP blockade, it differs from today's established treatments. The clinical results so far are promising, but the treatment is not yet approved and more research is needed to establish its long-term efficacy and safety. For patients, this development means that treatment options continue to expand – and that future obesity treatment has the potential to become both more effective and more individualized.

Sources

The New England Journal of Medicine (NEJM). Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial DOI: 10.1056/NEJMoa2504214

The New England Journal of Medicine (NEJM). Once-Weekly Semaglutide in Adults with Overweight or Obesity
https://www.nejm.org/doi/full/10.1056/NEJMoa2032183

The New England Journal of Medicine (NEJM). Tirzepatide Once Weekly for the Treatment of Obesity
https://www.nejm.org/doi/full/10.1056/NEJMoa2206038

European Medicines Agency (EMA). Wegovy
https://www.ema.europa.eu/en/medicines/human/EPAR/wegovy

European Medicines Agency (EMA). Mounjaro https://www.ema.europa.eu/en/medicines/human/EPAR/mounjaro

European Medicines Agency (EMA). Wegovy
https://www.ema.europa.eu/en/medicines/human/EPAR/wegovy

European Medicines Agency (EMA). Mounjaro https://www.ema.europa.eu/en/medicines/human/EPAR/mounjaro