With Pramlintide
Safety flag
Additive gastric-emptying delay, GI intolerance, and glucose lowering are plausible; a broad clinical contraindication is not established.
Interaction evidence source All research profiles
Investigational amylin analogue
Cagrilintide
Prepared by the ezGLP team. Sources last checked . Profile reviewed .
Routes represented in the knowledgebase: Subcutaneous (SubQ).
Educational overview
Investigational and not FDA-approved; FDA says it has not been found safe and effective for any condition and cannot lawfully be used in compounding.
Cagrilintide (development code NNC0174-0833) is an investigational long-acting analogue of amylin, the peptide hormone co-secreted with insulin by pancreatic beta cells that signals satiation, slows gastric emptying and suppresses glucagon after a meal. Native human amylin aggregates readily and has a very short half-life, so Novo Nordisk chemists redesigned the backbone with substitutions that block fibril formation and attached a fatty diacid chain that binds albumin. The resulting molecule is described as a non-selective agonist at amylin and calcitonin receptors, a class sometimes abbreviated DACRA, and its reported half-life of roughly a week supports once-weekly subcutaneous administration.
Human evidence comes from Novo Nordisk trials. A first-in-human programme and a 2021 Lancet phase 1 study examined cagrilintide given alongside semaglutide in healthy and overweight adults. The main monotherapy result is a phase 2 dose-finding trial published in the Lancet in 2021, in which 706 adults with overweight or obesity and without diabetes were randomised for 26 weeks and mean weight reductions reached about 10 percent at the highest dose against about 3 percent on placebo. Cagrilintide alone also formed a comparator arm in the phase 3 REDEFINE 1 trial, where it produced less weight loss than the combination with semaglutide.
Cagrilintide is not approved by the FDA, the European Medicines Agency or any other regulator, and no monotherapy marketing application has been announced; the sponsor's regulatory filings concern the fixed-dose combination with semaglutide. The FDA has stated that cagrilintide has not been found to be effective and acceptably safe for any condition, that it is not a component of an approved drug, and that it therefore cannot lawfully enter compounding in the United States. Powders sold by online vendors as cagrilintide, including material labelled for research use only, are unapproved drugs once offered for human use, and their identity and purity are unverified.
There is no approved product label, so no regulator-reviewed storage, reconstitution or in-use information exists outside a clinical trial protocol, where the sponsor supplies the peptide in a controlled cold chain. Material bought online is generally a lyophilised powder with vendor-supplied handling instructions and no established beyond-use period once dissolved. Amylin analogues are also sensitive to aggregation, which is the specific problem the molecule was engineered around, so handling conditions matter to whatever is actually in the vial. An inventory record that captures supplier, batch identifier, stated strength, reconstitution date, resulting concentration and storage temperature is the only trail a dose log leaves behind.
- Category
- Investigational amylin analogue
- Routes represented
- Subcutaneous (SubQ)
- Storage context
- Follow the dispensed product or pharmacy label; storage and beyond-use time vary by formulation.
Published literature
No verified PubMed or DOI link is available for this entry.
Safety evidence
Common or reported: nausea, constipation, diarrhea, injection-site reactions.
Investigational; long-term and rare adverse effects are not established.
Safety evidence sourceInteraction evidence
These are general, pairwise evidence notes. Green identifies the potential-synergy category, while Lv3/Lv2/Lv1 communicates evidence strength; it does not guarantee benefit or cancel a safety warning.
With semaglutide
Complementary evidenceLv3
Randomized human trials directly studied co-administered cagrilintide and semaglutide and found complementary weight and glycemic effects.
Interaction evidence sourcePhase 3 trialFDA unapproved GLP-1 warningCommon questions
What is cagrilintide and how does it work?
Cagrilintide is a long-acting synthetic analogue of amylin, a hormone released with insulin after meals. It activates amylin and calcitonin receptors in hindbrain regions such as the area postrema, which signal satiation, slow gastric emptying and suppress glucagon. Substitutions in the peptide prevent the fibril formation that makes natural amylin unstable, and an attached fatty diacid chain binds albumin, extending the half-life to roughly one week.
Is cagrilintide FDA approved?
No. Cagrilintide is investigational and has not been approved by the FDA, the European Medicines Agency or any other regulator, and no application for it as a single agent has been announced. The FDA states that it has not been shown effective and acceptably safe for any condition, is not a component of any approved drug, and cannot lawfully enter compounding in the United States.
How much weight did cagrilintide produce in trials?
In the 26-week phase 2 dose-finding trial of 706 adults with overweight or obesity and without diabetes, published in the Lancet in 2021, mean weight reduction reached about 10 percent at the highest dose studied compared with about 3 percent on placebo. In the phase 3 REDEFINE 1 trial the cagrilintide-alone arm produced less weight loss than the combination with semaglutide over 68 weeks.
How is cagrilintide different from a GLP-1 drug?
They target different receptor systems. GLP-1 receptor agonists such as semaglutide act on the incretin axis, increasing glucose-dependent insulin secretion and reducing appetite through GLP-1 receptors. Cagrilintide mimics amylin and signals through amylin and calcitonin receptors in the hindbrain. Trials that included both as separate arms found each reduced weight on its own, with larger reductions when the two were given together.
What side effects were reported with cagrilintide?
Gastrointestinal events were the most frequent findings in the phase 2 and phase 3 trials: nausea, vomiting, constipation and diarrhoea, generally mild to moderate and concentrated in the escalation period. Injection-site reactions were also reported. Because published exposure is limited to a few thousand participants over months rather than years, uncommon and long-term effects are uncharacterised, and no regulator has completed a safety review of the molecule.
Further reading
- Lau et al., Lancet 2021 (phase 2 dose-finding trial of once-weekly cagrilintide)
- Kruse et al., J Med Chem 2021 (development of cagrilintide, a long-acting amylin analogue)
- Enebo et al., Lancet 2021 (phase 1 cagrilintide with semaglutide)
- Garvey et al., N Engl J Med 2025 (REDEFINE 1, includes a cagrilintide-alone arm)
- Clin Pharmacokinet 2026 (cagrilintide pharmacokinetics in renal or hepatic impairment)
- ClinicalTrials.gov NCT03856047 (phase 2 cagrilintide study record)
- FDA, Concerns with unapproved GLP-1 drugs used for weight loss
Summarised from published literature for reference only, with citations to the source. Evidence is graded as reported and is not a recommendation to combine, dose, or use any compound.
For personal tracking and education only. Not medical advice, diagnosis, or treatment, and not a medical device. Peptides may be prescription-only or unapproved where you live. Consult a licensed healthcare professional.