Evidence map›Paper›PMID 40609154›Full record

ArticleEBioMedicine2025

Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3.

Alexandra Oliveira Carvas, Andrea Leuthardt, Patricia Kulka, Greta Lommi, Shad Hassan, Bernd Coester, Sofia Lundh, Tune Pers, Anna Secher, Kirsten Raun and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed.

  1. Trial
  2. Review
  3. Amylin: A Multi-Functional Pancreatic Hormone-A Review.Diabetes, obesity & metabolism · 2026
    Review
  4. Review
  5. Review
  6. Article
  7. The evolving landscape of obesity pharmacotherapy.Nature reviews. Drug discovery · 2026
    Review
  8. Article
  9. Article
  10. Article
  11. LEAP2 as a therapeutic target in obesity and cardiometabolic disorders.Reviews in endocrine & metabolic disorders · 2026
    Review
  12. Brain Amylin Signaling, Feeding, and Reward.Comprehensive Physiology · 2026
    Review
  13. Review
  14. Review
  15. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Alexandra Oliveira CarvasInstitute of Veterinary Physiology, University of Zurich, Switzerland.
Andrea LeuthardtInstitute of Veterinary Physiology, University of Zurich, Switzerland.
Patricia KulkaInstitute of Veterinary Physiology, University of Zurich, Switzerland.
Greta LommiInstitute of Veterinary Physiology, University of Zurich, Switzerland.
Shad HassanNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Bernd CoesterNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Sofia LundhGlobal Drug Discovery, Novo Nordisk A/S, Måløv, Denmark.
Tune PersNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Anna SecherGlobal Drug Discovery, Novo Nordisk A/S, Måløv, Denmark.
Kirsten RaunGlobal Drug Discovery, Novo Nordisk A/S, Måløv, Denmark.
Thomas A LutzInstitute of Veterinary Physiology, University of Zurich, Switzerland.
Christelle Le FollInstitute of Veterinary Physiology, University of Zurich, Switzerland. Electronic address: Christelle.lefoll@uzh.ch.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAmylin (AmyR) and calcitonin (CTR) receptor co-agonists are currently in Phase II/III clinical trials for obesity treatment. Amylin binds to a heterodimeric receptor composed of CTR and the receptor activity modifying proteins 1, 2 or 3 (RAMP1-3).

methodsWe investigated the role of amylin 1 and 3 (AMY

findingsBody weight loss was observed in WT cagrilintide-treated mice (-3.4 ± 0.51 g, P < 0.005; n = 8/group), whereas sCT rather increased it (0.60 ± 0.38 g, P < 0.01; n = 8/group). The absence of RAMP1 and RAMP3 impeded cagrilintide's potency but improved sCT's efficacy on weight loss. Cagrilintide and sCT both decreased food intake during the first few days of treatment in WT mice only (Day 1: vehicle 2.7 ± 0.2 g; cagrilintide 1.2 ± 0.1 g, P < 0.0001; sCT 1.5 ± 0.2 g, P < 0.0021; n = 7-8/group). Both peptides activated cFos signal in neurons of the dorsal vagal complex (DVC) and lateral parabrachial nucleus (LPBN) of WT mice while AP cFos signal was decreased in cagrilintide-treated RAMP1/3 KO mice by 57% compared to WT cagrilintide-injected mice (P < 0.001, n = 5-6/group). Differential gene expression was analysed in the DVC, LPBN and mediobasal hypothalamic area of WT and RAMP1/3 KO mice. After 3 weeks of treatment, neither sCT nor cagrilintide significantly altered gene expression in the DVC or LPBN in WT mice. However, mRNA bulk sequencing points to a role of RAMP1/3 in synaptic function and receptor trafficking.

interpretationAltogether, these results demonstrate the dependency of cagrilintide on AMY

fundingThis work was supported by an investigator led Novo Nordisk Consortium grant, Swiss National Foundation and the University of Zurich.

Indexed as

Body WeightBrainIslet Amyloid PolypeptideReceptor Activity-Modifying Protein 3Receptors, Islet Amyloid PolypeptideAnimalsCalcitoninDiet, High-FatMaleMiceMice, KnockoutObesityReceptor Activity-Modifying Protein 1Receptors, CalcitoninCalcitoninIslet Amyloid PolypeptideRamp1 protein, mouseReceptor Activity-Modifying Protein 1Receptor Activity-Modifying Protein 3Receptors, CalcitoninReceptors, Islet Amyloid Polypeptidesalmon calcitoninAmylinFood intakeHindbrainMouseWeight

Identifiers

PMID40609154
PMCPMC12270663

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.