CAGRILINTIDE

Cagrilintide is an investigational long-acting amylin analogue developed by Novo Nordisk for the treatment of obesity and overweight conditions. It is designed to be administered via subcutaneous injection once a week, typically in combination with semaglutide, a GLP-1 receptor agonist. This combination therapy, known as CagriSema, has demonstrated significant weight loss and improvements in cardiometabolic health in clinical trials.

Mechanism of Action

Cagrilintide mimics the natural hormone amylin, which is co-secreted with insulin from the pancreas. Amylin plays a role in regulating blood sugar levels and appetite. By acting on the brain’s appetite centers, cagrilintide helps to reduce food intake and promote satiety. This mechanism complements that of semaglutide, which enhances insulin secretion and reduces glucagon release, leading to improved glycemic control.()

Clinical Efficacy

In the REDEFINE 1 trial, a Phase III study involving 3,417 participants, the combination of cagrilintide and semaglutide resulted in a 20.4% reduction in body weight over 68 weeks. This was significantly greater than the 11.5% weight loss observed with cagrilintide alone, the 14.9% with semaglutide alone, and the 3.0% with placebo . Similarly, the REDEFINE 2 trial, which included 1,206 participants with type 2 diabetes, showed a 13.7% weight loss with the combination therapy compared to 3.1% with placebo.

Safety and Tolerability

Cagrilintide has been generally well-tolerated in clinical trials. The most common adverse events reported were gastrointestinal in nature, such as nausea and diarrhea, which are typical for medications affecting appetite and digestion. These side effects were mostly mild to moderate and decreased over time. Importantly, the combination of cagrilintide and semaglutide did not result in significant additional adverse effects compared to semaglutide alone.

Pharmacokinetics

Cagrilintide is administered once a week due to its long half-life of approximately 159–195 hours. After subcutaneous injection, it reaches peak plasma concentrations within 24 to 72 hours. The pharmacokinetic profile supports its use in combination with semaglutide, as the exposure to both drugs does not interfere with each other’s elimination.

Regulatory Status

As of now, cagrilintide is not approved for use and remains under investigation. Novo Nordisk is conducting further studies to confirm its long-term efficacy and safety profile. The promising results from the REDEFINE trials have generated significant interest in the potential of CagriSema as a treatment for obesity and overweight conditions.

Conclusion

Cagrilintide represents a novel approach in the pharmacological management of obesity, targeting appetite regulation through amylin receptor activation. When combined with semaglutide, it offers a potent therapeutic option with substantial weight loss and improvements in metabolic health. While further studies are needed to establish its long-term safety and efficacy, the current data suggest that cagrilintide has the potential to be a valuable addition to the arsenal of anti-obesity medications.