Metabolic · Amylin analog · Compounded 503A
Cagrilintide: amylin reborn as the GLP-1 partner.
Cagrilintide is a long-acting analog of amylin — the hormone co-secreted with insulin that controls satiety and slows gastric emptying. In Phase 3 trials (CagriSema), cagrilintide + semaglutide produced ~20% body weight reduction at 68 weeks. It is the most clinically advanced non-GLP-1 anti-obesity peptide.
What Cagrilintide is
Cagrilintide is a once-weekly amylin analog developed by Novo Nordisk. Amylin is a 37-amino-acid peptide hormone co-secreted with insulin from pancreatic beta cells that signals satiety and slows gastric emptying. Native amylin has a half-life of about 13 minutes — far too short to be a practical therapy.
Cagrilintide is engineered with a fatty-acid chain that binds albumin (similar to the strategy used in semaglutide and liraglutide), extending its half-life to enable once-weekly dosing. It activates both amylin and calcitonin receptors.
Cagrilintide alone produces meaningful weight loss; combined with semaglutide as 'CagriSema' it has produced the largest weight reductions of any approved or late-stage obesity drug — ~20% at 68 weeks in Phase 3, with full Phase 3 readouts continuing.
How it works
Cagrilintide activates amylin receptors in the area postrema of the hindbrain. This triggers satiety signaling and slows gastric emptying — producing earlier and longer-lasting fullness after meals. The amylin mechanism is distinct from the GLP-1 mechanism.
Because cagrilintide and GLP-1 receptor agonists work on different pathways (amylin/calcitonin vs incretin), their effects are additive. CagriSema combines the two and the weight-loss magnitude exceeds either drug alone — the largest pharmacological weight loss yet demonstrated in Phase 3 obesity trials.
Cagrilintide also has direct effects on bone homeostasis (via calcitonin receptor activity) and may produce a modest anti-resorptive effect on bone — a potentially favorable feature for women in menopause, though not the primary indication.
What patients use it for
Weight reduction
Cagrilintide alone produces 8–10% body weight reduction at 26 weeks. CagriSema (cagrilintide + semaglutide) produced ~20% body weight reduction at 68 weeks in the REDEFINE-1 Phase 3 trial.
GLP-1 synergy
The strongest case for cagrilintide is its complementary mechanism to GLP-1s. Patients who plateau on semaglutide alone often respond when cagrilintide is added.
Appetite regulation
Amylin signaling produces a distinct quality of satiety — earlier fullness and reduced inter-meal hunger. Many patients describe it as more 'natural' than GLP-1-only appetite suppression.
Once-weekly dosing
The fatty-acid linker gives cagrilintide a half-life that supports weekly subcutaneous injection — the same dosing rhythm as semaglutide for combined protocols.
Evidence summary
Cagrilintide is the most clinically advanced non-GLP-1 anti-obesity peptide. The REDEFINE-1 Phase 3 trial of CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg weekly) reported ~20% body weight reduction at 68 weeks (Novo Nordisk, 2024 readout).
Lau DCW et al. (Lancet, 2021) — Phase 2 of cagrilintide alone showed 8–10% weight loss at 26 weeks across a range of doses, with manageable GI tolerability.
Approval timeline: Novo Nordisk has submitted CagriSema for regulatory approval. In the U.S., compounded cagrilintide is used off-label by clinicians ahead of formal approval. This will likely change as the FDA pathway progresses.
Dosing and clinical context
General clinical context only. Kindr Health physicians determine the appropriate dose and protocol for each patient based on history and labs. This is not a prescription or dosing recommendation.
Cagrilintide is dosed subcutaneously once weekly with gradual titration — typically starting at 0.25 mg/week and stepping up over 12–16 weeks to the target dose (usually 1.2–2.4 mg/week depending on response).
When combined with semaglutide (CagriSema), the two are titrated in parallel — minimizing GI side effects by going slowly. The combined protocol is more demanding to manage than monotherapy and requires closer physician follow-up.
Standard protocols use cagrilintide as an adjunct to semaglutide rather than a replacement. Patients already on semaglutide who plateau are common candidates for adding cagrilintide.
Safety and contraindications
Most common side effects are gastrointestinal — nausea, decreased appetite, occasional vomiting or constipation. Generally milder than the GI profile of semaglutide alone in the published trials.
Contraindications mirror semaglutide: personal or family history of medullary thyroid carcinoma, multiple endocrine neoplasia type 2 (relative — discuss with physician), pregnancy, severe gastroparesis.
Off-label compounded use under physician supervision. CagriSema is in active FDA review; the regulatory landscape may shift.
Who it's typically considered for
- Adults with obesity or significant metabolic disease who have plateaued on GLP-1 monotherapy
- Patients seeking the largest pharmacological weight reduction currently demonstrated in Phase 3
- Patients comfortable with weekly subcutaneous injection and structured titration
- Patients in coordinated care with a physician — CagriSema is more complex than GLP-1 monotherapy
Frequently asked questions
What is CagriSema?
CagriSema is the combination of cagrilintide (a long-acting amylin analog) plus semaglutide (a GLP-1 receptor agonist) in once-weekly subcutaneous injection. In Phase 3 trials it produced approximately 20% body weight reduction at 68 weeks — the largest weight loss demonstrated by any anti-obesity medication in Phase 3.
Is cagrilintide FDA-approved?
Not yet in the United States. Novo Nordisk has submitted CagriSema for regulatory review. Currently, U.S. clinical use is via compounded cagrilintide from licensed 503A pharmacies under physician prescription for off-label use.
How is cagrilintide different from semaglutide?
They work through different receptors. Semaglutide is a GLP-1 receptor agonist (incretin pathway). Cagrilintide is an amylin/calcitonin receptor agonist (satiety + gastric emptying pathway). The two together produce additive weight loss — that's the entire premise of CagriSema.
Can I take cagrilintide alone or only with semaglutide?
Both. Cagrilintide monotherapy produces meaningful weight loss in trials (~8–10%). Most U.S. clinical protocols use it as an add-on to semaglutide for additional effect, but monotherapy is a valid path for patients who tolerate it well or cannot take GLP-1s.
How long until I see results?
Appetite changes are often noticeable within 1–2 weeks of starting (or up-titrating). Meaningful weight loss accrues over months. The Phase 3 trials measured 68-week endpoints because the trajectory continues for over a year.
Will cagrilintide affect my bone density?
Cagrilintide has activity at the calcitonin receptor, which is anti-resorptive on bone. The clinical magnitude of this effect is modest but potentially favorable, particularly for women in menopause who are otherwise concerned about bone loss with rapid weight reduction.
Can I use cagrilintide with HRT?
Yes. Cagrilintide and HRT address different systems and are commonly layered. Your kindr physician reviews your full medication list before prescribing.
Sources
- Lau DCW et al. 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 (2021). — www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01751-7/fulltext
- Frias JP et al. Efficacy and safety of co-administered once-weekly cagrilintide 2.4 mg with semaglutide 2.4 mg in type 2 diabetes (CagriSema). Lancet (2023). — www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01163-7/fulltext
- Novo Nordisk REDEFINE-1 Phase 3 results — CagriSema in adults with obesity (2024 readout). — www.novonordisk.com/news-and-media/news-and-ir-materials.html
- Hay DL et al. Amylin: pharmacology, physiology, and clinical potential. Pharmacological Reviews (2015). — pubmed.ncbi.nlm.nih.gov/26071095
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Medically reviewed by Dr. Ana Lisa Carr, MD, MBA
Board-Certified Family Medicine Physician · Lead Provider / Medical Reviewer
NPI 1689841744 · Last reviewed: May 10, 2026
Last reviewed May 10, 2026. Compounded medications are prepared by FDA-registered 503A pharmacies and are not FDA-approved drug products. Prescriptions require a clinical evaluation; a Kindr Health physician determines eligibility. Not for use in pregnancy. This page provides educational information and is not medical advice.