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Cagrilintide

From PeptidePlaza, the free peptide reference · Entry #031 · Metabolic · Hand-curated entry · Editorial standards

Research warning. Research chemical — not for human consumption. Cagrilintide is an investigational agent that has not received marketing approval anywhere as a monotherapy. Amylin receptor agonism markedly slows gastric emptying, which alters the absorption of anything else administered orally.

Cagrilintide (also known as AM833, NNC0174-0833, NN9838) is a metabolic research peptide. A lipidated amylin analogue engineered to resist the amyloid fibrillation that plagues native human amylin. Works on satiety pathways entirely separate from GLP-1 — which is why it stacks so effectively with semaglutide.

Cagrilintide is a long-acting analogue of amylin, the pancreatic β-cell hormone co-secreted with insulin that signals meal termination. Native human amylin is nearly unusable as a drug because it aggregates into amyloid fibrils; cagrilintide is built on a pramlintide-like 37-residue backbone with substitutions that suppress fibrillation, plus a C20 fatty diacid acylation via a γGlu-OEG spacer that gives albumin binding and once-weekly kinetics. It is a non-selective agonist at the amylin receptors (AMY1–3, calcitonin receptor + RAMP heterodimers) and the calcitonin receptor itself, with sub-nanomolar potency (AMY3 IC50 ≈ 170 pM; CTR IC50 ≈ 223 pM). In the phase 2 dose-finding programme cagrilintide monotherapy produced roughly 6–10% weight loss at 26 weeks; in the phase 3 REDEFINE 1 trial the 2.4 mg monotherapy arm reached approximately 11.5% at 68 weeks. Its real significance is mechanistic complementarity — amylin signalling acts through the area postrema and nucleus accumbens on satiation and food reward, pathways that only partly overlap with GLP-1, which is why the combination with semaglutide (CagriSema) outperforms either agent alone.

1 Mechanism of action

Agonises amylin receptors (AMY1–3, i.e. calcitonin receptor + RAMP1/2/3 complexes) and the calcitonin receptor in the area postrema and hypothalamus. Slows gastric emptying, suppresses postprandial glucagon, and enhances satiation and reduced food reward via hindbrain-to-hypothalamic circuits distinct from GLP-1 signalling.

Primary targets: AMY1 · AMY2 · AMY3 · Calcitonin receptor (CTR)

2 Reported effects

Effects below are those reported in the published literature cited on this page. They are not claims of clinical benefit and not medical advice.

2.1 Reported benefits

  • Once-weekly dosing from fatty-diacid acylation and albumin binding
  • ~11.5% mean weight reduction as monotherapy at 68 weeks (REDEFINE 1)
  • Satiety mechanism complementary to — not overlapping with — GLP-1 agonism
  • Slows gastric emptying and suppresses postprandial glucagon
  • Aggregation-resistant design avoids the amyloid fibrillation of native amylin

2.2 Side effects

  • Nausea, vomiting and other gastrointestinal effects (dose-dependent, usually transient)
  • Injection site reactions
  • Decreased appetite that can become excessive without monitoring
  • Constipation or diarrhoea
  • Hypoglycaemia risk when combined with insulin or sulfonylureas

3 Chemical and physical properties

CAS number1415456-99-3
Molar mass4409 g/mol
Purity (typical)>98%
Half-life~7–8 days (SC injection)
Storage−20 °C, lyophilised powder, desiccated
SolubilitySterile water / bacteriostatic water
Receptors / targetsAMY1, AMY2, AMY3, Calcitonin receptor (CTR)

3.1 Amino acid sequence

Lipidated 37-residue amylin analogue (pramlintide-derived backbone; intramolecular Cys2–Cys7 disulfide; Lys acylated with C20 fatty diacid via γGlu-OEG-OEG spacer)

4 Research dosages

Phase 2 dose-finding used 0.3, 0.6, 1.2, 2.4 and 4.5 mg SC weekly; phase 3 settled on 2.4 mg weekly after a 16–20 week escalation.

Dosages are reported from published protocols for reference only. Research chemicals are not for human consumption.

5 Research studies (8)

  1. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1)
    New England Journal of Medicine (2025) · RCT · N=3,417
    Phase 3 trial with cagrilintide 2.4 mg monotherapy, semaglutide 2.4 mg monotherapy, the combination, and placebo arms over 68 weeks.
    Key finding: Cagrilintide monotherapy produced ~11.5% weight loss at 68 weeks vs ~3.0% placebo — less than semaglutide alone but with additive effect in combination.
  2. Development of Cagrilintide, a Long-Acting Amylin Analogue
    Journal of Medicinal Chemistry (2021) · Preclinical · N/A (discovery)
    Medicinal chemistry paper describing the design strategy: backbone substitution to prevent fibrillation plus lipidation for protracted action.
    Key finding: Rational design solved amylin's amyloid-aggregation problem while achieving a half-life suitable for once-weekly dosing.
  3. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity.
    The New England journal of medicine (2025) · RCT
    Cagrilintide-semaglutide provided significant and clinically relevant body-weight reductions in adults with overweight or obesity, as compared with placebo.
  4. The promise of glucagon-like peptide 1 receptor agonists (GLP-1RA) for the treatment of obesity: a look at phase 2 and 3 pipelines.
    Expert opinion on investigational drugs (2025) · Review
    GLP-1-based therapies have changed the treatment of overweight/obesity.
  5. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes.
    The New England journal of medicine (2025) · RCT
    Once-weekly cagrilintide-semaglutide (at a dose of 2.4 mg each) resulted in a significantly lower body weight than placebo in adults with obesity and type 2 diabetes.
  6. Emerging pharmacotherapies for obesity: A systematic review.
    Pharmacological reviews (2025) · Systematic Review
    The history of antiobesity pharmacotherapies is marked by disappointments, often entangled with societal pressure promoting weight loss and the prevailing conviction that excess body weight signifies a lack of...
  7. Weight management treatment in obesity.
    Medicina clinica (2025) · Review
    Obesity is a chronic and relapsing disease associated with medical complications and mortality.
  8. Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis.
    BMJ (Clinical research ed.) (2024) · Systematic Review
    GLP-1RAs are efficacious in treating adults with type 2 diabetes.

6 Safety and risk profile

6.1 Regulatory status

Cagrilintide is currently classified as Phase 3 clinical trials. It has no approved human indication in the United States; availability elsewhere does not imply demonstrated safety or efficacy.

Safety score: 74/100 — low concern. Derived from clinical data volume, known risks and regulatory status.

6.2 Contraindications

Conditions and populations in which use is contraindicated:

  • Known hypersensitivity to amylin analogues
  • Gastroparesis or severe gastrointestinal motility disorder
  • History of pancreatitis (precautionary, class-wide)
  • Pregnancy or lactation (no safety data)
  • Concurrent insulin therapy without dose adjustment and glucose monitoring

6.3 Drug interactions

Drug or classInteractionRisk
Insulin / sulfonylureasAdditive glucose lowering — hypoglycaemia risk requires dose reduction of the secretagogue.High
Orally administered drugs (all classes)Delayed gastric emptying changes absorption rate and Cmax; critical for narrow-therapeutic-index oral drugs.Moderate
GLP-1 receptor agonistsAdditive appetite suppression and GI effects — the basis of CagriSema, but also compounds nausea and dehydration risk.Moderate

6.4 Long-term risks

  • No human data beyond ~2 years of continuous exposure
  • Loss of lean mass during rapid weight reduction
  • Unknown consequences of chronic calcitonin receptor agonism (bone turnover, calcium handling)
  • Nutritional deficiency with sustained appetite suppression

6.5 Research best practices

  • Store lyophilised powder at −20 °C; reconstituted solution at 2–8 °C
  • Escalate slowly — nausea is dose- and rate-dependent
  • Separate oral compounds in a protocol by several hours to control for delayed gastric emptying
  • Avoid repeated freeze-thaw cycles of reconstituted material
Safety data disclaimer. Safety assessments are based on published literature and are for educational reference only. Clinical evidence varies significantly between peptides. Always consult primary research and current regulatory guidance.

7 Frequently asked questions

How is cagrilintide different from a GLP-1 like semaglutide?
They act on different hormone systems. GLP-1 agonists work largely through GLP-1 receptors in the hypothalamus, brainstem and gut; cagrilintide mimics amylin, which signals satiation through the area postrema and also dampens food reward. Because the pathways only partly overlap, the effects add up rather than compete — the basis for the CagriSema combination.
Why can't native amylin be used as a drug?
Human amylin aggregates into amyloid fibrils, making it unstable in solution and difficult to formulate. Pramlintide solved this with proline substitutions but has a short half-life requiring dosing with every meal. Cagrilintide combines an aggregation-resistant backbone with fatty-acid acylation for once-weekly dosing.
How much weight loss does cagrilintide produce on its own?
In the REDEFINE 1 phase 3 trial, cagrilintide 2.4 mg alone produced roughly 11.5% mean weight loss at 68 weeks — meaningful, but below semaglutide monotherapy (~14.9%) and well below the combination (~20.4%).

8 References

  1. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. PubMed (2025). Garvey WT, et al.. View source
  2. The promise of glucagon-like peptide 1 receptor agonists (GLP-1RA) for the treatment of obesity: a look at phase 2 and 3 pipelines. PubMed (2025). Madsbad S, et al.. View source
  3. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. PubMed (2025). Davies MJ, et al.. View source
  4. Emerging pharmacotherapies for obesity: A systematic review. PubMed (2025). Kokkorakis M, et al.. View source

Related compounds

Entries that share a target, a mechanism, or a research area with Cagrilintide.

CagriSemapeptide blends

Also targets AMY1

The first amylin + GLP-1 fixed-dose combination to reach phase 3. Two satiety systems in one weekly injection, and the closest any injectable has come to bariatric-surgery-range weight loss.

Liraglutideapproved

Shares agonises and glp-1 pharmacology

The GLP-1 that proved the class. A C16 palmitoyl chain gave native GLP-1 a 13-hour half-life instead of two minutes — and produced the first cardiovascular outcome data for the family.

Semaglutideapproved

Shares glp-1 and hypothalamus pharmacology

A long-acting GLP-1 analog distinguished by its C18 fatty diacid chain, enabling albumin binding and a half-life of ~7 days. One of the most clinically studied peptides in modern metabolic research.

Survodutidemetabolic

Shares glucagon and glp-1 pharmacology

A 29-amino-acid dual agonist that pairs GLP-1 appetite suppression with glucagon-driven energy expenditure and hepatic fat oxidation. Its liver-fat data is the standout: up to 63% reduction.

Davalintidemetabolic

Shares calcitonin and amylin pharmacology

Davalintide is a calcitonin gene-related peptide type 1 receptor agonist and an amylin receptor AMY1, CALCR/RAMP1 agonist.

Teduglutideapproved

Shares agonises and area pharmacology

A single amino acid substitution turns GLP-2 from a 7-minute hormone into a drug that regrows intestinal villi. The only approved peptide that makes the gut physically bigger.

9 See also

For research reference only. Not medical advice. Peptides may be regulated or restricted in your jurisdiction. Entry validated by the PeptidePlaza Biomedical Research Desk; see editorial standards.