Cagrilintide
Cagrilintide (Long-Acting Amylin Analog)
A long-acting amylin analog that suppresses appetite through a completely different brain pathway than GLP-1 drugs, making it a powerful add-on to existing weight loss medications.
Cagrilintide is a long-acting version of amylin, a hormone your pancreas naturally releases alongside insulin every time you eat. Amylin's job is simple: it tells your brain that you have had enough to eat. The problem is that the natural version breaks down in your body within minutes, so it does not last long enough to make a sustained impact on appetite. Cagrilintide is engineered to last 7 to 8 days, which is why you only need one injection per week. Think of it as a louder, clearer version of a fullness signal your body already produces.
What makes cagrilintide truly exciting is that it works through a completely different part of the brain than GLP-1 drugs like semaglutide and tirzepatide. Those drugs target the hypothalamus, which controls your overall drive to seek food throughout the day. Cagrilintide targets the brainstem, which controls the immediate feeling of being full during a meal. Because these are two separate systems with no overlap, adding cagrilintide to a GLP-1 drug gives your brain the fullness message through two independent channels instead of one.
The clinical results back this up. In the REDEFINE 1 trial, the combination of cagrilintide plus semaglutide produced over 20% average weight loss, with 60% of participants losing 20% or more and 23% losing 30% or more. Those are among the most significant results seen with any anti-obesity medication to date. Cagrilintide is currently in Phase 3 clinical trials and is not yet FDA approved, but it is available through research peptide suppliers.
How It Works
Your appetite is controlled by two separate systems in your brain, and understanding this is key to understanding why cagrilintide is so valuable. The first system lives in the hypothalamus, which acts like your appetite thermostat. It controls how much you think about food throughout the day, how strong your cravings are, and how often you feel the urge to eat. GLP-1 drugs like semaglutide and tirzepatide turn down this thermostat. The second system lives in the brainstem, in an area called the area postrema, and it works more like a satiety switch. It detects what is happening in your stomach right now and tells you when to put the fork down during a meal.
Here is the critical detail: the neurons that respond to amylin in the brainstem do not even have GLP-1 receptors on them. They are completely separate systems. So if you have been taking semaglutide for months and your GLP-1 receptors have developed some tolerance, your amylin receptors have not been touched at all. Cagrilintide activates these untouched receptors with a signal that is much stronger and longer-lasting than what your body produces naturally, cutting through any amylin resistance that may have developed from metabolic dysfunction.
There is also a vicious cycle that cagrilintide helps break. As metabolic health declines and insulin resistance develops, your body pumps out more insulin to compensate. Because amylin gets released alongside insulin, chronically elevated insulin means chronically elevated amylin, which causes your amylin receptors to become desensitized. This means your natural fullness signal gets weaker just when you need it most. Cagrilintide breaks through this resistance because it is engineered to be so much stronger and more stable than natural amylin. Combined with a GLP-1 drug, you get your appetite thermostat turned down and your satiety switch working properly again at the same time.
Potential Benefits
Dramatically Enhanced Weight Loss in Combination
The REDEFINE 1 trial showed CagriSema produced 20.4% average weight loss over 68 weeks, with 60% of participants losing 20% or more and 23% losing 30% or more. These are among the strongest results published for any anti-obesity medication.
Effective on Its Own
Even without a GLP-1 drug, cagrilintide alone produced 10.8% weight loss at the 4.5 mg dose over 26 weeks in Phase 2 trials, which actually outperformed the FDA-approved drug liraglutide head to head.
Completely Different Mechanism Than GLP-1 Drugs
If you have tried semaglutide, tirzepatide, or retatrutide and still struggle with hunger, cagrilintide works through the amylin pathway in a different part of the brain. Your amylin receptors have not been exposed to any of those GLP-1 compounds, making cagrilintide a true add-on rather than a replacement.
Blood Sugar Improvements
In the REDEFINE 2 trial with type 2 diabetes patients, 73.5% of CagriSema participants achieved an HbA1c of 6.5% or less, compared to just 15.9% with placebo. The combination also returned 88% of prediabetic participants to normal blood sugar levels.
Once-Weekly Convenience
The long half-life of about 7 to 8 days means you inject once per week, making it easy to pair with your existing weekly GLP-1 injection schedule.
What the Research Shows
The Phase 2 monotherapy trial, published in The Lancet in 2021, enrolled 706 participants with obesity and tested cagrilintide at various doses for 26 weeks. The results showed clear dose-dependent weight loss: 6.0% at 0.3 mg, 9.0% at 1.2 mg, 9.7% at 2.4 mg, and 10.8% at 4.5 mg, compared to 3.0% for placebo. At the highest dose, cagrilintide actually outperformed liraglutide 3.0 mg, an FDA-approved weight loss drug, head to head. A Phase 1b combination trial in 2021 showed that adding cagrilintide 2.4 mg to semaglutide 2.4 mg produced 17.1% weight loss in just 20 weeks, compared to about 10% with semaglutide alone.
The REDEFINE 1 trial, a major Phase 3 study published in the New England Journal of Medicine in 2025, enrolled 3,417 adults without diabetes. The combination of cagrilintide 2.4 mg plus semaglutide 2.4 mg, known as CagriSema, produced 20.4% average weight loss over 68 weeks. Semaglutide alone produced 14.9% and cagrilintide alone produced 11.5%. Among CagriSema participants, 60% lost 20% or more of their body weight, and 23% lost 30% or more. When accounting for full treatment adherence, weight loss with CagriSema reached 22.7%. Remarkably, 56.4% of CagriSema participants were no longer classified as obese by the end of the study, and 88% of those with prediabetes returned to normal blood sugar levels.
The REDEFINE 2 trial, also published in the New England Journal of Medicine in 2025, studied 1,206 adults with type 2 diabetes. CagriSema produced 13.7% weight loss compared to 3.4% for placebo, and 73.5% of CagriSema participants achieved an HbA1c of 6.5% or lower compared to just 15.9% with placebo. The lower weight loss in the diabetes population is consistent across all GLP-1 trials, as people with type 2 diabetes tend to lose less weight due to underlying metabolic differences.
What to Know
Nausea is the most common side effect, along with vomiting, constipation or diarrhea, abdominal discomfort, decreased appetite, and feeling overly full. When combining cagrilintide with a GLP-1 compound, these gastrointestinal effects tend to be more pronounced, especially during the early titration phase.
Less common effects include headache, dizziness, injection site reactions, and mild hypoglycemia, which is more likely when combined with a GLP-1 compound. These typically resolve on their own and do not require stopping treatment.
Those with a history of pancreatitis, gallbladder disease, gastroparesis or other GI motility disorders, kidney disease, or type 1 diabetes should use cagrilintide with caution and close monitoring. When combined with insulin or sulfonylureas, those medication doses may need reduction to prevent low blood sugar. Not studied in pregnant or breastfeeding women and should be avoided during pregnancy.
Seek immediate medical attention for persistent vomiting that does not resolve, severe abdominal pain which could indicate pancreatitis or gallbladder issues, signs of allergic reaction such as rash, swelling, or difficulty breathing, signs of severe dehydration, or blood sugar below 70 mg/dL with symptoms.
Research References
Once-weekly cagrilintide for weight management in people with overweight and obesity
Lau DCW, Erichsen L, Francisco-Ziller N, et al. · The Lancet · 2021
Phase 2 trial with 706 participants demonstrating dose-dependent weight loss up to 10.8% at the 4.5 mg dose over 26 weeks, outperforming liraglutide 3.0 mg head to head.
View StudySafety, tolerability, pharmacokinetics, and pharmacodynamics of cagrilintide with semaglutide
Enebo LB, Berthelsen KK, Kankam M, et al. · The Lancet · 2021
Phase 1b combination trial showing that cagrilintide 2.4 mg plus semaglutide 2.4 mg produced 17.1% weight loss over 20 weeks, significantly more than semaglutide alone at approximately 10%.
View StudyCoadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1)
Garvey WT, Frias JP, Jastreboff AM, et al. · New England Journal of Medicine · 2025
Phase 3 trial with 3,417 adults showing CagriSema produced 20.4% average weight loss over 68 weeks, with 60% losing 20% or more and 23% losing 30% or more of body weight.
View StudyCagrilintide-semaglutide in adults with overweight or obesity and type 2 diabetes (REDEFINE 2)
Davies MJ, Aroda VR, Collins BS, et al. · New England Journal of Medicine · 2025
Phase 3 trial with 1,206 adults with type 2 diabetes showing CagriSema produced 13.7% weight loss and 73.5% of participants achieved HbA1c of 6.5% or less over 68 weeks.
View StudyDevelopment of cagrilintide, a long-acting amylin analogue
Kruse T, Hansen JL, Vestermark GL, et al. · Journal of Medicinal Chemistry · 2021
Detailed the molecular engineering behind cagrilintide, explaining how modifications to natural amylin created a compound with a 7 to 8 day half-life suitable for once-weekly dosing.
View Study