Cagrilintide (AM833): Research, Mechanism & Current Evidence

What is Cagrilintide?

Cagrilintide is a long-acting synthetic version of amylin, a hormone released by the pancreas alongside insulin. It is being developed by Novo Nordisk, both on its own and combined with semaglutide in a fixed combination known as CagriSema.

It is investigational. No amylin analogue of this type is currently approved for weight management.

Status: Investigational. Not approved.

What is Cagrilintide researched for?

Trials have focused on body weight in obesity, and on whether combining an amylin analogue with a GLP-1 receptor agonist produces a larger effect than either alone.

Blood sugar control in type 2 diabetes is a secondary research question.

• Phase 3 trials demonstrate significant weight loss.
• 22.7% weight loss with CagriSema combination, surpassing existing therapies.
• 15.7% weight loss in diabetic patients with concurrent glycemic improvements.
• 2.2% HbA1c reduction with CagriSema versus semaglutide alone.
• Amylin receptor activation enhances insulin sensitivity and glucose metabolism.
• Dual pathway satiety via amylin and calcitonin receptor activation.

How does Cagrilintide work?

Amylin is released with insulin after eating and contributes to feeling full. Cagrilintide acts on the same receptors — the amylin and calcitonin receptors — but is chemically modified with a fatty acid chain so it stays in circulation long enough for weekly dosing.

Because amylin and GLP-1 signal fullness through different routes, the research rationale for combining them is that the effects may add rather than overlap.

Reported targets: calcitonin receptor, Amylin receptor

What does the research show?

Phase 2 work reported meaningful weight reduction with cagrilintide alone, and larger reductions when combined with semaglutide. The CagriSema phase 3 programme, REDEFINE, has reported results that were widely discussed as falling short of pre-trial expectations, which is a useful reminder that phase 2 figures often shrink at phase 3.

Anti-drug antibodies have been reported in a substantial proportion of participants, though without a clear effect on how well the compound worked.

Limitations of the current evidence

The combination has more published data than cagrilintide alone, so it can be difficult to separate what the amylin component contributes.

Long-term safety and durability data are not yet available.

References

1. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity

   Garvey WT, Blüher M, Osorto Contreras CK, et al. · The New England journal of medicine · 2025

   Phase 3a REDEFINE 1 trial: 3,417 adults without diabetes. Estimated mean weight loss -20.4% with CagriSema vs -3.0% placebo at 68 weeks. GI adverse events in 79.6% of treatment group, mainly transient and mild-to-moderate.

   PMID 40544433

2. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes

   Davies MJ, Bajaj HS, Broholm C, et al. · The New England journal of medicine · 2025

   Phase 3a REDEFINE 2 trial: Adults with BMI ≥27, HbA1c 7-10%, and type 2 diabetes. Mean weight loss -13.7% with CagriSema vs -3.4% placebo at 68 weeks. Significant improvements in glycemic measures.

   PMID 40544432

3. Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial

   Frias JP, Deenadayalan S, Erichsen L, et al. · Lancet (London, England) · 2023

   32-week phase 2 trial at 17 US sites. CagriSema showed greater weight loss vs semaglutide or cagrilintide alone. HbA1c improvements significant. Well tolerated with predominantly GI adverse events.

   Controlled clinical trial · PMID 37364590

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