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Study · Animal study (in vivo) · mouse · 2025

7 results

Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3.

Carvas AO, Leuthardt A, Kulka P, Lommi G, Hassan S, Coester B, Lundh S, Pers T, Secher A, Raun K, Lutz TA, Le Foll C

EBioMedicine3 Jul 2025Cited by 19 (Europe PMC)

PMID40609154 (opens in a new tab)PMCIDPMC12270663 (opens in a new tab)DOI10.1016/j.ebiom.2025.105836 (opens in a new tab)PepBankPUB-40609154
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Summary

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 (AMY1R, AMY3R) receptors in modulating the pharmacological effects of the dual amylin-calcitonin receptor agonists, cagrilintide and salmon calcitonin (sCT), in RAMP1/3 knockout (KO) mice. Male wild-type (WT) and KO littermate mice were fed high-fat diet for 23 weeks prior to the 3-week treatment period with vehicle, 150 nmol/kg sCT or 3 nmol/kg cagrilintide (subcutaneously, SID).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 AMY1R and AMY3R to lower body weight.FundingThis work was supported by an investigator led Novo Nordisk Consortium grant, Swiss National Foundation and the University of Zurich.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

7 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In high-fat diet-fed wild-type mice, cagrilintide caused body weight loss over 3 weeks.

    In plain wordsIn mice on a high-fat diet, cagrilintide caused body weight loss over 3 weeks.

    Peptide
    Cagrilintide
    Outcome
    DecreaseBody weight change in wild-type mice
    Study

    mousen = 8

    High-fat diet-fed male wild-type mice
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    3 nmol/kg · subcutaneous · 3 weeksAs given in this study (mouse).

    Measurements

    Body weight change
    −3.4 g
    wild-type mice, cagrilintide

    Source sentences

    Summary
    Body weight loss was observed in WT cagrilintide-treated mice (-3.4 ± 0.51 g, P < 0.005; n = 8/group)
    1 context sentence
    Summary · context
    Male wild-type (WT) and KO littermate mice were fed high-fat diet for 23 weeks prior to the 3-week treatment period with vehicle, 150 nmol/kg sCT or 3 nmol/kg cagrilintide (subcutaneously, SID).
  2. 02AnimalAnimal study (in vivo)Mechanism

    In RAMP1/RAMP3 knockout mice, the potency of cagrilintide for body weight loss was reduced compared with wild-type mice.

    In plain wordsIn mice lacking RAMP1 and RAMP3, cagrilintide was less able to lower body weight than in normal mice.

    Peptide
    Cagrilintide
    Outcome
    DecreaseBody weight loss in RAMP1/3 knockout mice
    Study

    mousen: not reported in source

    High-fat diet-fed male wild-type and RAMP1/3 knockout mice
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    3 nmol/kg · subcutaneous · 3 weeksAs given in this study (mouse).

    Source sentences

    Summary
    The absence of RAMP1 and RAMP3 impeded cagrilintide's potency but improved sCT's efficacy on weight loss.
    1 context sentence
    Summary · context
    Male wild-type (WT) and KO littermate mice were fed high-fat diet for 23 weeks prior to the 3-week treatment period with vehicle, 150 nmol/kg sCT or 3 nmol/kg cagrilintide (subcutaneously, SID).
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In wild-type mice, cagrilintide decreased food intake during the first few days of treatment (day 1: 1.2 g versus 2.7 g with vehicle).

    In plain wordsIn mice, cagrilintide lowered food intake in the first days of treatment compared with vehicle.

    Peptide
    Cagrilintide
    Outcome
    DecreaseFood intake in wild-type mice (day 1)
    Study

    mousen: not reported in source

    High-fat diet-fed male wild-type and RAMP1/3 knockout mice
    Comparator
    Vehicle
    Outcome group
    Appetite and food intake · Metabolic and weight
    Studied dose
    3 nmol/kg · subcutaneous · 3 weeksAs given in this study (mouse).

    Measurements

    Food intake day 1
    1.2 g
    wild-type mice, cagrilintide
    Food intake day 1
    2.7 g
    wild-type mice, vehicle

    Source sentences

    Summary
    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).
    1 context sentence
    Summary · context
    Male wild-type (WT) and KO littermate mice were fed high-fat diet for 23 weeks prior to the 3-week treatment period with vehicle, 150 nmol/kg sCT or 3 nmol/kg cagrilintide (subcutaneously, SID).
  4. 04AnimalAnimal study (in vivo)Mechanism

    In RAMP1/RAMP3 knockout mice, cagrilintide did not decrease food intake; the decrease occurred in wild-type mice only.

    In plain wordsIn mice lacking RAMP1 and RAMP3, cagrilintide did not lower food intake, unlike in normal mice.

    Peptide
    Cagrilintide
    Outcome
    No significant changeFood intake in RAMP1/3 knockout mice
    Study

    mousen: not reported in source

    High-fat diet-fed male wild-type and RAMP1/3 knockout mice
    Comparator
    Vehicle
    Outcome group
    Appetite and food intake · Metabolic and weight
    Studied dose
    3 nmol/kg · subcutaneous · 3 weeksAs given in this study (mouse).

    Source sentences

    Summary
    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).
    1 context sentence
    Summary · context
    Male wild-type (WT) and KO littermate mice were fed high-fat diet for 23 weeks prior to the 3-week treatment period with vehicle, 150 nmol/kg sCT or 3 nmol/kg cagrilintide (subcutaneously, SID).
  5. 05AnimalAnimal study (in vivo)Mechanism

    In wild-type mice, cagrilintide activated cFos signal in neurons of the dorsal vagal complex and lateral parabrachial nucleus.

    In plain wordsIn mice, cagrilintide switched on a marker of nerve cell activity in two brain areas.

    Peptide
    Cagrilintide
    Outcome
    IncreasecFos activation in dorsal vagal complex and lateral parabrachial nucleus
    Study

    mousen: not reported in source

    High-fat diet-fed male wild-type and RAMP1/3 knockout mice
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    3 nmol/kg · subcutaneous · 3 weeksAs given in this study (mouse).

    Source sentences

    Summary
    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).
    1 context sentence
    Summary · context
    Male wild-type (WT) and KO littermate mice were fed high-fat diet for 23 weeks prior to the 3-week treatment period with vehicle, 150 nmol/kg sCT or 3 nmol/kg cagrilintide (subcutaneously, SID).
  6. 06AnimalAnimal study (in vivo)Mechanism

    In RAMP1/RAMP3 knockout mice, area postrema cFos signal after cagrilintide was 57% lower than in wild-type mice given cagrilintide.

    In plain wordsIn mice lacking RAMP1 and RAMP3, cagrilintide produced a weaker brain activity signal in the area postrema than in normal mice.

    Peptide
    Cagrilintide
    Outcome
    DecreaseArea postrema cFos signal in RAMP1/3 knockout mice
    Study

    mousen: not reported in source

    High-fat diet-fed male wild-type and RAMP1/3 knockout mice
    Comparator
    Wild-type mice given cagrilintide
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    3 nmol/kg · subcutaneous · 3 weeksAs given in this study (mouse).

    Measurements

    Area postrema cFos signal decrease
    57%
    RAMP1/3 knockout vs wild-type, cagrilintide

    Source sentences

    Summary
    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).
    1 context sentence
    Summary · context
    Male wild-type (WT) and KO littermate mice were fed high-fat diet for 23 weeks prior to the 3-week treatment period with vehicle, 150 nmol/kg sCT or 3 nmol/kg cagrilintide (subcutaneously, SID).
  7. 07AnimalAnimal study (in vivo)Mechanism

    In wild-type mice, 3 weeks of cagrilintide did not significantly alter gene expression in the dorsal vagal complex or lateral parabrachial nucleus.

    In plain wordsIn mice, 3 weeks of cagrilintide did not significantly change gene activity in two brain areas.

    Peptide
    Cagrilintide
    Outcome
    No significant changeGene expression in dorsal vagal complex and lateral parabrachial nucleus
    Study

    mousen: not reported in source

    High-fat diet-fed male wild-type and RAMP1/3 knockout mice
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    3 nmol/kg · subcutaneous · 3 weeksAs given in this study (mouse).

    Source sentences

    Summary
    After 3 weeks of treatment, neither sCT nor cagrilintide significantly altered gene expression in the DVC or LPBN in WT mice.
    1 context sentence
    Summary · context
    Male wild-type (WT) and KO littermate mice were fed high-fat diet for 23 weeks prior to the 3-week treatment period with vehicle, 150 nmol/kg sCT or 3 nmol/kg cagrilintide (subcutaneously, SID).

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 3Current

    27 Oct 2026, 16:35 UTC

    Study data updated · source update from Europe PMC

  2. Version 2

    9 Oct 2026, 18:17 UTC

    Study results updated

  3. Version 1

    9 Oct 2026, 03:04 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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