By Dr. Asnat Raziel, bariatric surgeon specializing in obesity treatment, metabolic health and healthy longevity; Director of the Multidisciplinary Center for Obesity Treatment, Assia Medical, Assuta Ramat HaChayal, Tel Aviv
Amylin and obesity: the satiety hormone from the pancreas
The link between amylin and obesity has become one of the hottest topics in obesity research. Amylin is a hormone the pancreas releases together with insulin every time we eat. Its main job is to tell the brain it is time to stop. That is why drug companies are now developing medications that mimic it, either on their own or combined with GLP-1 drugs.
In this article, I explain what the hormone amylin is, how it works in the body and what the research shows so far. I also cover what is already available and what is still being studied.
What amylin is and where it is made
Amylin is a small hormone made up of 37 amino acids. It is produced by the beta cells of the pancreas, which release insulin at the same moment. The two hormones enter the bloodstream together, at a ratio of roughly one hundred insulin molecules for every amylin molecule. In other words, amylin is insulin’s small, quiet partner.
People with diabetes are deficient in amylin, especially those with type 1 diabetes, in whom the beta cells barely function. But amylin’s story goes well beyond diabetes. In recent years, researchers have focused instead on its effects on appetite and body weight.
How amylin works in the body
Most of amylin’s effects pass through the area postrema, a small region of the brainstem that senses what is happening in the blood. Its receptors are made of the calcitonin receptor paired with a helper protein called RAMP. A comprehensive review of how amylin works summarizes four main effects:
- Satiety: amylin signals to the brain that the body has had enough food, so the meal ends sooner.
- Slower stomach emptying: food stays in the stomach longer, so the feeling of fullness lasts.
- Glucagon suppression: after a meal, amylin suppresses glucagon, a hormone that raises blood sugar.
- Energy expenditure: according to the review, amylin also increases the body’s energy expenditure.
Note the difference between amylin and GLP-1. Both hormones promote satiety, but they act through different receptors and different pathways in the brain. That is what makes combining them so interesting: each one applies its own brake on appetite. It is part of a broader picture of satiety hormones that is changing the way we treat obesity.
What’s more, drugs that act on the brain’s satiety system may also affect “food noise,” the constant, intrusive thoughts about food. Research on this in amylin-based drugs is still in its early days.
Amylin and obesity: why the natural hormone doesn’t work as a drug
If amylin is so effective, why not simply inject it? First, natural amylin acts in the body for only a very short time. Second, human amylin molecules tend to stick to one another and form sticky protein deposits (amyloid). Deposits like these are found in the pancreas of many people with type 2 diabetes.
Because of these two problems, researchers developed amylin analogs: molecules similar to the natural hormone, but stable and long-lasting. Some of them work in the body for a full week.
Pramlintide: the first amylin-based drug
The first drug of this kind is pramlintide, sold as Symlin. The FDA approved it about twenty years ago for type 1 and type 2 diabetes, as an add-on to insulin. Pramlintide is short-acting, so it is injected before meals.
According to the review, pramlintide improves blood sugar control after meals without increasing the risk of low blood sugar or weight gain. However, the FDA did not approve it for treating obesity. The real breakthrough came only with the long-acting analogs.
The new generation: amylin and obesity trials
The new drugs work for a full week, so a single weekly injection is enough. Four molecules currently stand out. None of them has yet been approved for treating obesity.
CagriSema: amylin and GLP-1 together
CagriSema combines two drugs in a single injection: cagrilintide, a long-acting amylin analog, and semaglutide, the active ingredient in Wegovy. The REDEFINE 1 trial enrolled 3,417 adults with obesity or overweight who did not have diabetes. After 68 weeks, they lost an average of 20.4% of their body weight, compared with 3.0% in the placebo group.
By comparison, cagrilintide alone led to a loss of 11.5%, and semaglutide alone to 14.9%. In other words, amylin adds substantial weight loss on top of GLP-1. A detailed breakdown of all the trials appears in my review of the REDEFINE trials. Novo Nordisk submitted CagriSema to the FDA for approval in December 2025, but at the time of writing no decision has been made. The drug is not available in Israel.
Eloralintide: amylin alone, once a week
Eloralintide, from Lilly, acts mainly on one type of amylin receptor. A phase 2 trial enrolled 263 adults with obesity or overweight who did not have diabetes. After 48 weeks, the higher doses led to an average weight loss of up to 20%, compared with 0.4% on placebo. The most common side effects were nausea and fatigue.
This showed that an amylin analog on its own, without GLP-1, can achieve major weight loss. I have also written on the site about combining eloralintide with tirzepatide.
Petrelintide: moderate weight loss and good tolerability
Zealand and Roche are developing petrelintide. The ZUPREME-1 trial enrolled 493 people with overweight or obesity. After 42 weeks, average weight loss reached up to 10.7%, compared with 1.7% on placebo. Most side effects were gastrointestinal, and most were mild. The companies therefore plan to test it in combination with another drug as well.
Amycretin: one molecule, two mechanisms
Amycretin, from Novo Nordisk, now officially named zenagamtide, activates both GLP-1 receptors and amylin receptors. In an early-stage study, a weekly injection of 20 mg led to a 22.0% weight loss after 36 weeks, and a 60 mg dose to 24.3%. However, this was a small study, with 125 participants and a high dropout rate, so larger trials are needed to confirm the results.
Side effects and safety
Like GLP-1 drugs, amylin-based drugs mainly cause digestive side effects: nausea, vomiting, constipation and diarrhea. In REDEFINE 1, for example, 79.6% of participants on CagriSema reported such an effect, compared with 39.9% on placebo. Most effects were mild to moderate and eased over time.
Participants on eloralintide also reported fatigue. It is important to remember that these trials lasted only about a year to a year and a half. There are therefore no data yet on safety over many years, nor on effects on heart attacks or strokes. A large trial of CagriSema and the heart is currently underway.
Amylin and obesity in the clinic: what it means for you today
At the time of writing, no amylin-based drug has been approved for treating obesity, either in Israel or in the United States. So there is no reason to search for “amylin” online or buy it from unregulated sources. Such products are not quality-controlled, and there is no way to know what they contain.
Meanwhile, existing drug treatment, with GLP-1 medications such as Wegovy and Mounjaro, achieves good results. In our clinic, we choose treatment based on weight, underlying conditions, personal preferences and response to treatment. When amylin-based drugs arrive, they may add an important option. If you want to dig deeper, you can read about the next generation of these drugs.
The bottom line
Amylin is a natural satiety hormone that the pancreas releases together with insulin. It slows stomach emptying, suppresses glucagon and tells the brain to stop eating. In trials, new drugs that mimic it led to weight loss of about 10% to 20%, and even more when combined with GLP-1. Ultimately, the link between amylin and obesity opens up a promising treatment direction, but these drugs are still awaiting approval.
The information in this article is general and does not replace personal medical advice.
Frequently asked questions
What is the link between amylin and obesity?
Amylin promotes satiety and slows stomach emptying. As a result, drugs that mimic it reduce how much people eat and lead to weight loss.
Is there an amylin-based weight-loss drug in Israel?
No. At present, no such drug has been approved in Israel. CagriSema is awaiting an FDA decision in the United States.
What is the difference between amylin and GLP-1?
Both hormones promote satiety, but through different receptors and pathways in the brain. In addition, amylin comes from the pancreas, whereas GLP-1 comes mainly from the intestine.
Amylin and obesity: does diet affect the hormone?
No research shows that any particular food or supplement significantly raises amylin. However, meals rich in protein and dietary fiber contribute to satiety through other mechanisms.
References
Amylin: From Mode of Action to Future Clinical Potential in Diabetes and Obesity
Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity
Amylin Analogue Boosts Weight Loss When Added to GLP-1
New Amylin-Based Agonists for the Treatment of Obesity and Type 2 Diabetes Mellitus
