CagriSema – combination treatment under development for weight loss

What is CagriSema?

CagriSema is a combination treatment in clinical development consisting of semaglutide and cagrilintide. It represents an advancement within pharmacological treatment of obesity by combining mechanisms of action from different hormone systems, with the goal of achieving an additive or potentially synergistic effect.

Semaglutide is a well-studied substance used in approved medications for the treatment of type 2 diabetes and obesity. It mimics the body's own GLP-1 hormone and affects both appetite regulation and blood sugar control.

Cagrilintide is a synthetic analog of the hormone amylin, which is normally released from the pancreas alongside insulin in connection with meals. Amylin contributes to the regulation of satiety, gastric emptying, and blood sugar levels after food intake.

By combining these two substances in a single treatment, multiple physiological signaling pathways that govern energy intake and metabolism can be influenced.

How does CagriSema work?

CagriSema works by modulating the body's appetite and satiety systems via both central (brain) and peripheral (gastrointestinal tract) mechanisms.

Semaglutide (GLP-1 receptor agonist):

• Stimulates satiety signals in the central nervous system, particularly in the hypothalamus
• Delays gastric emptying
• Improves glucose control through glucose-dependent insulin release and reduced glucagon secretion

Cagrilintide (amylin analog):

• Enhances satiety signals
• Inhibits glucagon release after meals
• Dampens blood sugar spikes after food intake
• Delays gastric emptying via complementary mechanisms

The combined effect is a reduced energy intake, primarily through increased and more sustained satiety, which facilitates an energy deficit and thereby weight loss.

CagriSema: clinical studies

Results from major Phase 3 studies, REDEFINE 1 and REDEFINE 2, published in the New England Journal of Medicine, show that CagriSema can contribute to significant weight loss in individuals with overweight or obesity.

In REDEFINE 1, where participants did not have type 2 diabetes, an average weight loss of approximately 20 percent was observed after 68 weeks of treatment. The effect of the combination of semaglutide and cagrilintide was more pronounced than with the individual substances alone. In REDEFINE 2, which included people with type 2 diabetes, the weight loss was approximately 14 percent. In both studies, the results were clearly superior compared to placebo.

The effect lies in the upper range of what current pharmacological treatments can achieve for obesity. At the same time, it is important to remember that results can vary between individuals, and comparisons between different treatments should be interpreted with caution, as studies may differ in design and patient population.

Is CagriSema approved?

No, CagriSema is currently not approved for the treatment of overweight or obesity and is therefore not yet available as a routine treatment.

Weight loss and health effects

Weight loss is often associated with several positive health effects beyond changes in body weight. For many, this includes improvements in metabolic functions, such as more stable blood sugar levels and a more favorable lipid profile.

Significant weight loss can also contribute to improvements in weight-related conditions, such as high blood pressure and sleep apnea, which can be significant for overall health and quality of life.

To optimize the treatment effect, it is recommended that pharmacological treatment be combined with sustainable lifestyle habits. A nutrient-dense diet with a tailored energy intake and adequate protein intake, in combination with regular strength training, can help preserve muscle mass during weight loss.

Who can benefit from pharmacological treatment for obesity?

Drug treatment for obesity can be an alternative for individuals who have not achieved sufficient results through lifestyle changes alone, or who have an increased health risk linked to their weight.

The treatment is typically aimed at adults with a BMI over 30, or individuals with a BMI over 27 in combination with at least one weight-related complication such as type 2 diabetes, high blood pressure, or elevated blood lipids.

The purpose of the treatment is not only to reduce body weight but also to improve metabolic health and reduce the risk of secondary diseases. For many, medication can serve as support in creating and maintaining sustainable changes in diet and lifestyle.

Which treatment is appropriate is always determined individually in consultation with healthcare professionals, taking into account both medical conditions and personal goals.

Frequently Asked Questions about CagriSema and Novo Nordisk's research (FAQ)

What side effects can the treatment cause? 

In studies, it was observed that the most common side effects were related to the gastrointestinal tract. These included nausea, vomiting, diarrhea, constipation, and abdominal pain. The symptoms were of mild to moderate severity.

Will the medication come in the form of a tablet or an injection? 

CagriSema is being developed as a treatment administered via injection under the skin (subcutaneous injection), typically once a week.

Can I get CagriSema prescribed by a doctor?

 CagriSema is not yet approved for the treatment of overweight or obesity and therefore cannot be prescribed at this time. However, approved medications, such as semaglutide and tirzepatide, are available within evidence-based treatment for obesity.

Do I still need to change my lifestyle habits?

 Yes, pharmacological treatment for obesity works best in combination with sustainable lifestyle habits. The treatment can make it easier to reduce energy intake through increased satiety and reduced cravings, but long-term results are built on habits that can be maintained over time.

A nutritious diet with adequate protein intake and regular physical activity, including strength training, contributes to preserving muscle mass and supporting the body's function during weight loss. The treatment is therefore seen as a support—not a replacement—for lifestyle changes.

What do the REDEFINE 1 and REDEFINE 2 studies involve in the research on CagriSema?

The REDEFINE 1 and REDEFINE 2 studies are two large phase 3 studies that form part of the clinical research on CagriSema. The purpose of the studies is to investigate effectiveness and safety in the treatment of overweight and obesity as well as type 2 diabetes.

The studies have been conducted over 68 weeks and together include several thousand participants:

• REDEFINE 1 included people with overweight or obesity without type 2 diabetes
• REDEFINE 2 included people with overweight or obesity with type 2 diabetes

In both studies, CagriSema was compared with placebo, and in REDEFINE 1 also with the individual components (semaglutide and cagrilintide).

The results show that the treatment leads to clear weight loss and improvements in metabolic parameters. The combination of two hormonal mechanisms of action may provide greater effect than individual treatments.

Sources

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

The New England Journal of Medicine (NEJM). Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity
https://www.nejm.org/doi/full/10.1056/NEJMoa2502081

The New England Journal of Medicine (NEJM). Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes https://www.nejm.org/doi/full/10.1056/NEJMoa2502082

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