Cagrilintide Side Effects

Researchers are particularly interested in side effects, considering the novel composition of this peptide and its significant potential across multiple research areas, such as chronic pain management, weight loss, and glycemic control in type 2 diabetes.

In this post, we will walk you through primary and secondary side effects and ways to minimize health-related risks during treatment.

What is Cagrilintide?

Cagrilintide is a new synthetic peptide analog of the human hormone amylin. Amylin is a 37-amino-acid peptide that the pancreas co-secrets with insulin and promotes satiety, slow gastric emptying, and suppresses glucagon after a meal.

This peptide targets an amylin receptor, which is part of a class of receptors that respond to calcitonin and calcitonin-related peptides. A Danish pharmaceutical company, Novo Nordisk, first developed this peptide to boost the natural effects of amylin in activating the previously mentioned receptors, reducing appetite, and managing glucose levels.

The primary therapeutic application of Cagrilintide is focused on weight management and treating obesity-related conditions such as type 2 diabetes. While not yet approved by the FDA, this peptide has passed phase 3 of clinical trial, and in combination with Semaglutide, it tends to treat various metabolic disorders.

How Does Cagrilintide Work?

Cagrilintide helps with weight management through several different actions. The digestive system – specifically the stomach and intestines – slows down how quickly food moves through. This slower movement tells the body it’s full, which helps reduce appetite and leads to less eating. Because food takes longer to pass through, sugar is absorbed more gradually, as well. This helps prevent sudden spikes in blood sugar, giving the body more time to manage it before it gets stored as fat.

This peptide also influences the brain directly. Animal studies have shown that there are amylin receptors in a part of the brain called the arcuate nucleus. When Cagrilintide binds to these receptors, it affects other areas like the brainstem and pituitary gland, which work together to increase feelings of fullness and reduce the urge to eat.

Lastly, Cagrilintide acts in the pancreas in a way that’s similar to the hormone amylin. It helps reduce the release of glucagon – a hormone that normally raises blood sugar. With less glucagon in the system, the body is less likely to turn excess sugar into fat.

Side effects

Cagrilintide is still in clinical development as of 2024 and has not been approved for public use. It’s currently being evaluated in Phase 3 studies, often in combination with Semaglutide. Nevertheless, earlier studies (Phases 1 and 2) have shown encouraging signs – it’s quite well-tolerated and has the same safety profile as other drugs in the amylin class, e.g., pramlintide.

The most common side effects noted to date have been gastrointestinal, specifically nausea and constipation. These are to be expected, as amylin analogs like Cagrilintide naturally delay food movement through the stomach.

Most side effects were temporary and well-tolerated. In fact, the dropout rate due to side effects was low – about 10%.

In a Phase 2 study of 706 obese or overweight patients, side effects were seen at all dose levels (0.3 to 4.5 mg weekly). If the patients were given the highest dose (4.5 mg/week), 88% experienced side effects. They were mainly gastrointestinal, and only one patient in that group discontinued due to side effects.

The following is a list of the most common side effects in patients receiving the highest dose:

Nausea (47%)

Nearly half of the patients reported nausea. It is the most frequent complaint and is because Cagrilintide slows down digestion. Since food stays in the stomach longer, it can cause queasiness. Fortunately, nausea tends to improve as the body adapts over time.

Fatigue (20%)

Fatigue or feeling more tired than usual was also a reported side effect. It could be due to reduced calorie intake, a change in blood sugar control, or adjustment of the body to the drug.

Constipation (21%)

Cagrilintide slows food movement through your digestive system, a boon to losing weight but a source of constipation. This can be remedied by drinking more water, eating food with fiber, and exercising regularly.

Allergic Reactions (10%)

Some subjects experienced mild allergic reactions such as itching or skin rash. These were not common and not too serious. Nevertheless, signs of serious allergic reactions must not be disregarded.

Vomiting (8%)

Less common than nausea, vomiting can also result, particularly when the body is getting used to the medication. Decreasing the dose in most cases can fix this.

Headaches (7%)

Some participants experienced mild headaches resulting from dehydration or the body’s adjustment to dietary and hormonal changes.

Loose Stools (7%)

Although Cagrilintide has the effect of slowing down digestion, some people had the opposite reaction – looser stools. This was a less common effect and not usually serious.

Dyspepsia (4%)

Indigestion or bloating was also a side effect, likely because of the drug’s action on the digestive process. Eating smaller meals and avoiding oily or spicy foods can help.

Severe Side Effects of Cagrilintide

Most people can take Cagrilintide without issue, but some rare but potentially severe side effects have been reported in clinical trials. The incidence is infrequent and does not seem to be dose related.

Infrequent serious Events (2-7%)

In the largest phase 2 trial, severe side effects in those on Cagrilintide occurred between 2% and 7%. This was slightly greater than in the other groups: 4% with liraglutide and 3% on placebo. Therefore, although rare, severe side effects are not Cagrilintide- specific.

Gallbladder Issues (Cholelithiasis)

One of the serious cases with a potential connection to Cagrilintide was gallstone formation (cholelithiasis). This occurred in one of the volunteers on 4.5 mg weekly. While an isolated event, it emphasizes the need for caution, especially on increased dosing.

Antibody Development

A few patients developed anti-Cagrilintide antibodies on treatment. The probability of this happening was greater with more intense dosing and more prolonged treatment. By week 26, 46% to 73% of the users had developed the antibodies.

However, the antibodies did not seem to influence weight loss results or allergic reactions. So, while present, they did not appear to be impacting the extent to which the drug was effective.

Is it safe?

This peptide is a synthetic analogue of amylin, a naturally occurring protein released by the pancreas. Bearing in mind all side effects, this peptide does not pose a long-term threat to human health. Even though its benefits are currently theoretical, we also believe that its side effects are of a theoretical nature. This area of research is currently under investigation, and if you decide to use Cagrilintide, make sure to consult with your healthcare provider to determine further steps.

References:

1. Dehestani, B., Stratford, N. R., & le Roux, C. W. (2021). Amylin as a Future Obesity Treatment. Journal of Obesity & Metabolic Syndrome, 30(4), 320–325. https://doi.org/10.7570/jomes21071
2. Frias, J. P., Nauck, M. A., Van J., Kutner, M. E., Cui, X., Urva, S., Gimeno, R. E., & Bettencourt, R. (2021). Efficacy and Safety of the Amylin Analog Cagrilintide Alone and in Combination With Semaglutide in Patients With Type 2 Diabetes: A Randomized Clinical Trial. JAMA, 326(10), 934–945. https://doi.org/10.1001/jama.2021.12299
3. Müller, T. D., Finan, B., Bloom, S. R., D'Alessio, D., Drucker, D. J., Flatt, P. R., Fritsche, A., Gribble, F. M., Habener, J. F., Holst, J. J., Langhans, W., Meier, J. J., Nauck, M. A., Schwartz, T. W., Seeley, R. J., Theodorakis, M. J., Zierath, J. R., & Tschöp, M. H. (2019). Glucagon-like peptide 1 (GLP-1). Molecular Metabolism, 30, 72–130. https://doi.org/10.1016/j.molmet.2019.09.010
4. Urva, S., Betts, K. A., Qiao, Q., Van J., Gimeno, R. E., & Frias, J. P. (2023). Cagrilintide: An Amylin Analog With Potential in Obesity Management. Obesity (Silver Spring), 31(2), 325–336. https://doi.org/10.1002/oby.23651
5. Knudsen, L. B., & Lau, J. (2019). The Discovery and Development of Liraglutide and Semaglutide. Frontiers in Endocrinology, 10, 155. https://doi.org/10.3389/fendo.2019.00155
6. Eržen, S., Tonin, G., Jurišić Eržen, D., & Klen, J. (2024). Amylin, Another Important Neuroendocrine Hormone for the Treatment of Diabesity. International journal of molecular sciences, 25(3), 1517. https://doi.org/10.3390/ijms25031517
7. National Library of Medicine (U.S.). (n.d.). A research study to see how much CagriSema lowers blood sugar and body weight compared to placebo in people with type 2 diabetes treated with once-daily basal insulin with or without metformin (REIMAGINE 3). Identifier NCT06323161. https://clinicaltrials.gov/study/NCT06323161
8. Lau, D. C. W., Erichsen, L., Francisco, A. M., Satylganova, A., le Roux, C. W., McGowan, B., Pedersen, S. D., Pietiläinen, K. H., Rubino, D., & Batterham, R. L. (2021). Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. Lancet (London, England), 398(10317), 2160–2172. https://doi.org/10.1016/S0140-6736(21)01751-7