Cagrilintide is a long-acting synthetic version of amylin-a naturally occurring peptide released with insulin. It has shown great promise in animal testing as a drug for both type 2 diabetes and obesity. Researchers have also looked at using it to treat liver disease-alcohol-related liver damage-and cardiovascular disease.
There is also some interest on whether or not this peptide might be used in the therapy of Alzheimer’s disease, but to date, no concrete studies have been published in that field. The majority of the research has been focused on combining cagrilintide with semaglutide, particularly in the treatment of obesity and type 2 diabetes. Combined, these products seem to produce stronger and longer-lasting effects of weight loss.
But although early results in preclinical studies are encouraging, human studies are only in their initial stages. More clinical trials need to be done before we can say this peptide is effective and safe to use.
Origin of Cagrilintide: What is Amylin?
Amylin, or islet amyloid polypeptide (IAPP), is a peptide that pancreatic beta cells co-secrete with insulin. Scientists discovered
that Amylin has a significant action in the brain, where it sends a signal of fullness and satiety. Amylin is initially made as an 89-amino-acid propeptide but is processed in the body to an active molecule containing just 37 amino-acids-at a ratio of about 100:1 to insulin.
This compound has a number of functions. It slows gastric emptying, enhances feelings of fulness, and regulates blood sugar levels after a meal. This activity helps the body use glucose as a fuel source rather than storing it as fat.
In addition, amylin affects bone metabolism. It works together with hormones such as calcitonin and CGRP, which take part in body calcium regulation. These hormones deposit calcium into bones and are able to reduce calcium loss via kidneys. While the full extent of its action is still being studied, Amylin is known to help maintain bone density and avert bone breakdown.
When the amylin-causing gene is deactivated in animal studies, researchers observe decreased appetite and overall calorie intake. Amylin would normally be broken down by the same enzymes responsible for breaking down insulin. Cagrilintide was created to resist these enzymes, which resulted in a longer duration of action and greater potency when administered in research.
Cagrilintide mechanism of action?
How does cagrilintide work? Cagrilintide peptide has several effects upon the body. In the gastrointestinal system-i.e., the stomach and intestines-it slows the movement of food. The slowed transit stimulates the gastrointestinal system to send signals to the brain that the body is full. This shortens appetite and decreases food intake. It also induces decreased sugar uptake, which works to decrease high blood sugar levels. This gives the body a longer time to burn glucose and reduces the likelihood of sugar being stored as fat.
In addition to its use in the digestive process, cagrilintide also has a direct action on the central nervous system. Studies in mice found that the brain’s arcuate nucleus contains many amylin receptors. When cagrilintide is activated on these receptors, it impacts locations like the brain stem and the pituitary gland. This activity tends to increase the feeling of fullness and reduces the drive for hunger.
Lastly, cagrilintide also affects the pancreas. In the same manner that natural amylin does, it is part of a feedback system that limits how much glucagon will be released. This serves to slow down the conversion of glucose into fat.
What is cagrilintide used for?
Cagrilintide and Obesity Research
Two significant clinical trials have examined the impact of cagrilintide on weight reduction, and both provide useful insights into how the peptide works. In the first trial, patients who received a weekly injection of cagrilintide lost weight of about 6% to 11% of body weight in just six weeks. These outcomes were substantially improved over the placebo group and even above the outcome of liraglutide, which was used as a positive control. To the researcher’s surprise, side effects observed were identical for cagrilintide compared to liraglutide.
The second study examined the effect of combining cagrilintide with semaglutide. In combination, they produced a stronger weight loss reaction than when administered separately. This led researchers to believe that the two peptides are likely to work in a synergistic fashion. The findings showed an impressive loss of 17.1 % weight after 20 weeks. In perspective, a person weighing 200 pounds would be expected to lose around 34 pounds within a period of five months using this combination.
Cagrilintide in Diabetes Management
Cagrilintide, along with other like peptides including pramlintide, has shown potential in helping improve insulin sensitivity and reduce hemoglobin A1C levels. This is accomplished by lessening the release of glucagon, which is a key player in blood sugar regulation. Trials have reported an A1C reduction of 2.2 % in a relatively short time of being on peptide-based treatment like these.
One of the key benefits of cagrilintide is that it can be administered weekly. This reduced frequency should improve patient compliance as well as overall therapeutic efficacy. With its long half-life, cagrilintide maintains stable blood glucose levels over longer periods.
Cagrilintide in Alzheimer’s Disease
For many years scientists have known about a link between glucose control in the blood and mental impairment. For example, individuals with diabetes will experience memory, attention, and processing speed deficits even at a younger age. Hyperglycemia, or elevated blood sugar, has been found to trigger cytotoxic responses like the activation of protein kinase C, which can directly cause brain cell death. It also contributes to increased inflammation and oxidative stress, both of which may accelerate cognitive decline and induce other diabetes complications such as cardiovascular disease and renal disease.
Several studies still verify the connection between blood glucose and brain activity. Although both low and high levels of glucose are toxic to the brain, there is most evidence supporting a more persistent threat from high blood sugar. In one longitudinal study of older women, chronically high blood glucose was linked with an increased risk of developing mild cognitive impairment and dementia.
In a surprising turn of events, the same research suggests that elevated blood sugar levels may reduce available glucose to the brain. Since the brain is dependent almost solely upon glucose for its energy requirements, the disruption can be especially crippling. Other research supports that insulin resistance in the brain is the main cause behind cognitive challenges noted with diabetes. Together, the evidence indicates that if the brain cannot properly process glucose-even when blood glucose levels are high-this inability to properly metabolize energy might be a cause of dementia.
Other research has also been done on amylin’s function in the brain. Like glucose, excessive or deficient amounts of amylin in the blood might influence cognitive function negatively. The Framingham Heart Study found that there was a U-shaped correlation between amylin levels and cognitive functions, with high or low levels at both extremes being associated with a greater risk of cognitive decline and Alzheimer's disease.
References:
- Kruse, T., Lerche Hansen, J., Dahl, K., Schäffer, L., & Sensfuss, U. (2021). Development of Cagrilintide, a long‑acting amylin analogue. Journal of Medicinal Chemistry, 64(23), 17138–17150. https://doi.org/10.1021/acs.jmedchem.1c00565
- Lau, D. C. W., Erichsen, L., Francisco, A. M., Satylganova, A., Le Roux, C. W., Francisco, A. M., … Knop, F. K. (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. The Lancet, 397(10286), 1736–1748. https://doi.org/10.1016/S0140‑6736(21)01751‑7
- Davies, M. J., Bajaj, H. S., Broholm, C., Eliasen, A., Garvey, W. T., Le Roux, C. W., … Pedersen, S. D. (2025). Coadministration of cagrilintide and semaglutide in adults with overweight or obesity and type 2 diabetes. New England Journal of Medicine, 393(26), 2441–2452. https://doi.org/10.1056/NEJMoa2502082
- Olsson, M., Herrington, M. K., Reidelberger, R. D., Permert, J., & Arnelo, U. (2007). Food intake and meal pattern in IAPP knockout mice with and without infusion of exogenous IAPP. Peptides, 28(7), 1416–1423. https://doi.org/10.1016/j.peptides.2007.06.011
- Westermark, P., & Westermark, G. T. (2004). Amylin inhibits bone resorption while the calcitonin receptor controls bone formation in vivo. Journal of Cell Biology, 164(4), 509–515. https://doi.org/10.1083/jcb.200310103
- Yaffe, K., Blackwell, T., Kanaya, A. M., Davidowitz, N., Barrett‑Connor, E., & Krueger, K. (2004). Diabetes, impaired fasting glucose, and development of cognitive impairment in older women. Neurology, 63(4), 658–663. https://doi.org/10.1212/01.WNL.0000134666.64593.BA
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