Cagrilintide.
Cagrilintide (development code AM833) is a long-acting, once-weekly synthetic analogue of the pancreatic hormone amylin, developed by Novo Nordisk.
Cagrilintide (development code AM833) is a long-acting, once-weekly synthetic analogue of the pancreatic hormone amylin, developed by Novo Nordisk. Cagrilintide is in human trials, and PepCue grades its published evidence C tier (53/100). Also known as amylin analog. This is a research reference, not medical or dosing advice.
What it is
Cagrilintide (development code AM833) is a long-acting, once-weekly synthetic analogue of the pancreatic hormone amylin, developed by Novo Nordisk. It is a "dual amylin and calcitonin receptor agonist" (DACRA)-class peptide engineered with a lipidation (fatty-acid acylation) that prolongs its half-life, and is being investigated for chronic weight management in adults with overweight or obesity, both as a monotherapy and as the amylin component of the fixed-dose combination CagriSema (with semaglutide).
How it works
Native amylin is co-secreted with insulin from pancreatic beta cells and reduces food intake by promoting meal-ending satiety, slowing gastric emptying, and suppressing glucagon. Cagrilintide mimics this by activating amylin and calcitonin receptors, which are heterodimers of the calcitonin receptor with receptor-activity-modifying proteins (RAMPs). Preclinical work in RAMP1/RAMP3 knockout mice (eBioMedicine, 2025) indicates cagrilintide's weight-lowering effect is mediated largely through brain amylin receptors 1 and 3 in hindbrain and hypothalamic circuits that govern appetite. Because amylin signaling is mechanistically distinct from GLP-1, combining the two (as in CagriSema) is intended to engage complementary satiety pathways and produce additive weight loss.
Mechanism pathways
Activating amylin and calcitonin-family receptors to promote meal-ending satiation.
Amylin, also called islet amyloid polypeptide, is co-secreted with insulin from pancreatic beta cells in response to a meal. It does not act through a dedicated single receptor. Instead, amylin receptors are heterodimers formed when the calcitonin receptor associates with one of three receptor-activity-modifying proteins, known as RAMP1, RAMP2, and RAMP3. The pairing changes the receptor's pharmacology, so the same core receptor becomes amylin-responsive depending on which accessory protein it partners with. These complexes are concentrated in hindbrain structures, particularly the area postrema and nucleus tractus solitarius, and in hypothalamic circuits. Activating them produces satiation rather than appetite suppression in the broader sense. The distinction matters. Amylin signalling is the physiological brake that ends a meal, reducing the size of individual eating occasions and slowing gastric emptying, and it also suppresses glucagon after eating. Preclinical work suggests amylin signalling additionally influences leptin sensitivity, which is interesting because leptin resistance is one of the standard explanations for why weight regain is so common. Native amylin is impractical as a drug: it is prone to aggregating into insoluble fibrils, which is the same tendency that produces amyloid deposits in the pancreas in type 2 diabetes. Analogs are therefore engineered for solubility and stability, and long-acting versions add modifications that extend circulation time enough for infrequent administration. Compounds in this group differ mainly in that engineering and in whether they are used alone or paired with a GLP-1 receptor agonist in a fixed combination. The reason for combining the two is that amylin and GLP-1 act on overlapping but distinct circuits, so their effects on food intake can add together rather than simply duplicating each other. That is the explicit design logic behind the combination products in this group. The pathway's clinical standing is intermediate. Amylin biology itself is well established, and an earlier short-acting amylin analog has been an approved medicine for years, so the mechanism is not speculative. The long-acting analogs described here, however, are still working through late-stage clinical development, and their durable benefit and tolerability relative to GLP-1 agonism alone are not yet settled questions. Nausea and vomiting are recognised features of amylin receptor activation, reflecting the same hindbrain circuitry that produces the satiation effect, so the wanted and unwanted effects are not easily separated.
The evidence
Human data are now substantial for the combination and growing for monotherapy. The pivotal phase 3 REDEFINE 1 trial in over 3,400 adults with overweight/obesity without diabetes (NEJM 2025, PMID 40544433) reported mean weight loss of roughly 20.4% with CagriSema, 11.8% with cagrilintide monotherapy, 14.9% with semaglutide, and about 3% with placebo at 68 weeks; cagrilintide thus produced clinically meaningful weight loss on its own, though less than the combination. REDEFINE 2 studied CagriSema in type 2 diabetes, and additional REDEFINE/REIMAGINE program trials (e.g., REIMAGINE 2 in The Lancet Diabetes & Endocrinology, 2026) extend the dataset. The brain-receptor mechanism evidence (eBioMedicine, PMID 40609154) is preclinical (mouse), so the molecular target attribution should not be read as proven in humans; most large efficacy data describe the semaglutide combination rather than cagrilintide alone.
The evidence, in brief
A long-acting amylin analogue (Novo Nordisk) for weight management. A randomized, placebo- and active-controlled phase-2 dose-finding trial showed significant, dose-dependent weight reduction with good tolerability; it is real human evidence, still pre-approval.
- Lau DCW et al.: Once-weekly cagrilintide for weight management: phase 2 trialLancet, 2021 (PMID 34798060)
Evidence maturity
An evidence-only reading: approval status, human vs preclinical data, mechanism and safety. Popularity never raises it. Research file #009
Some human signal atop preclinical work; gaps remain.
Studied in human clinical trials; evidence is meaningful.
Claim receipts
Popular claims about Cagrilintide, checked against the state of the evidence. The verdict describes evidence maturity, never an invented study result.
Phase 3 data reported clinically meaningful weight loss for monotherapy against placebo.
In the same Phase 3 program, monotherapy weight loss was lower than the semaglutide arm.
It is investigational and not approved as a standalone product; the filing covers the combination.
Trial tolerability was consistent with the class, but long-term and cardiovascular outcome data are not yet available.
Safety profile
In the REDEFINE program the safety profile of cagrilintide and CagriSema was reported as broadly consistent with incretin/amylin-based therapies, with predominantly mild-to-moderate gastrointestinal effects (nausea, vomiting, diarrhea, constipation) as the most common adverse events, generally most pronounced during dose escalation. Long-term safety, cardiovascular outcomes, and the safety of cagrilintide as a standalone therapy are not yet fully characterized in published phase 3 data, and head-to-head long-term comparisons remain limited. As an investigational agent, cagrilintide has no established safety profile for use outside of controlled clinical trials; material sold as research-only "cagrilintide" is not a regulated medicine and carries unknown identity, purity, and contamination risks.
Compound notes
- Cagrilintide is a long-acting amylin analog. Amylin is a hormone co-secreted with insulin that affects satiety and gastric emptying.
- It is investigational and studied for weight management, notably combined with semaglutide (the CagriSema program).
- Investigational; not FDA-approved.
- Efficacy and safety are still being established in trials.
Regulatory status
Cagrilintide is investigational and not approved by the FDA as a standalone drug. Novo Nordisk submitted an NDA for the CagriSema combination (cagrilintide plus semaglutide) for weight management on December 18, 2025; as of mid-2026 it remains under FDA review and is not yet approved.
Investigational, currently in registered human clinical trials.
By the numbers
- 01Long-acting (once-weekly), lipidated amylin analogue; Novo Nordisk code AM833
- 02Belongs to the dual amylin and calcitonin receptor agonist (DACRA) class
- 03Is the amylin half of CagriSema, paired with the GLP-1 agonist semaglutide
- 04Phase 3 REDEFINE 1 (NEJM 2025): ~11.8% mean weight loss as monotherapy vs ~20.4% for the combination at 68 weeks
- 05Mechanism attributed to brain amylin receptors 1 and 3 in preclinical mouse studies
- 06CagriSema NDA filed Dec 2025; not FDA-approved as of mid-2026
Cagrilintide: research formats
Choose the format you are researching to see route-specific notes.
Long-acting lipidated amylin analog given once weekly in trials. Not approved as a standalone drug.
Cagrilintide is a once-weekly lipidated amylin analog studied both as a monotherapy and as the amylin half of the fixed-dose combination CagriSema. It is investigational, so there is no marketed standalone presentation and no labeled titration schedule.
The fatty-acid acylation is what makes weekly administration possible; it slows clearance of a hormone analog that would otherwise be far shorter-acting.
Novo Nordisk filed an NDA for the CagriSema combination in December 2025. Cagrilintide alone remains unapproved.
Sources
Every factual claim above resolves to a real, published source.
- Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1)New England Journal of Medicine, 2025, PMID 40544433
- Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3EBioMedicine, 2025, PMID 40609154 (preclinical, mouse)
- Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2)The Lancet Diabetes & Endocrinology, 2026, PMID 42251859
- Novo Nordisk files for FDA approval of CagriSema (NDA submission announcement)Novo Nordisk company announcement, December 18, 2025
Cite this page
PepCue. “Cagrilintide: the evidence.” PepCue, reviewed June 1, 2026. https://www.pepcue.app/p/cagrilintide.
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