Cagrilintide and retatrutide combination therapy enhances weight loss and metabolic outcomes in obese male rats.

Petersen J, Merrild C, Holm SK, Kurgan N, Hassan S, Mathiesen CV, Börchers S, Svendsen C, D'Anna S, Andersen NR, Klein AB, Fritzen AM, Deshmukh AS, Pers TH, Clemmensen C

Nature metabolism15 Sept 2026

PMID42744908DOI10.1038/s42255-026-01603-yPepBankPUB-42744908

Publisher page PubMedAsk about this study

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Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study16

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

01AnimalAnimal study (in vivo)Efficacy outcome
In diet-induced obese male rats, daily co-administration of cagrilintide and retatrutide produced dose-dependent reductions in body weight that exceeded equimolar monotherapies and matched-dose semaglutide or tirzepatide combinations.
In plain wordsIn obese male rats, cagrilintide plus retatrutide lowered body weight more than either drug alone or semaglutide or tirzepatide combinations.
Peptide
Cagrilintide
Outcome
DecreaseBody weight
Study
ratn: not reported in source
Diet-induced obese male rats
Comparator
Equimolar monotherapies and matched-dose semaglutide or tirzepatide combinations
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Daily co-administration produces dose-dependent reductions in body weight and food intake that exceed both equimolar monotherapies and matched-dose comparator combinations incorporating semaglutide or tirzepatide.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we demonstrate enhanced metabolic benefits of a combination therapy with retatrutide, a unimolecular GLP-1R/GIPR/GCGR tri-agonist, and cagrilintide, an AMLNR/CALCR co-agonist, in diet-induced obese male rats.
Report a problemFND-4274490801
02AnimalAnimal study (in vivo)Efficacy outcome
In diet-induced obese male rats, daily co-administration of retatrutide and cagrilintide produced dose-dependent reductions in body weight that exceeded equimolar monotherapies and matched-dose semaglutide or tirzepatide combinations.
In plain wordsIn obese male rats, retatrutide plus cagrilintide lowered body weight more than either drug alone or semaglutide or tirzepatide combinations.
Peptide
Retatrutide
Outcome
DecreaseBody weight
Study
ratn: not reported in source
Diet-induced obese male rats
Comparator
Equimolar monotherapies and matched-dose semaglutide or tirzepatide combinations
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Daily co-administration produces dose-dependent reductions in body weight and food intake that exceed both equimolar monotherapies and matched-dose comparator combinations incorporating semaglutide or tirzepatide.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we demonstrate enhanced metabolic benefits of a combination therapy with retatrutide, a unimolecular GLP-1R/GIPR/GCGR tri-agonist, and cagrilintide, an AMLNR/CALCR co-agonist, in diet-induced obese male rats.
Report a problemFND-4274490802
03AnimalAnimal study (in vivo)Efficacy outcome
In diet-induced obese male rats, daily co-administration of cagrilintide and retatrutide produced dose-dependent reductions in food intake that exceeded equimolar monotherapies and matched-dose semaglutide or tirzepatide combinations.
In plain wordsIn obese male rats, cagrilintide plus retatrutide reduced food intake more than either drug alone or semaglutide or tirzepatide combinations.
Peptide
Cagrilintide
Outcome
DecreaseFood intake
Study
ratn: not reported in source
Diet-induced obese male rats
Comparator
Equimolar monotherapies and matched-dose semaglutide or tirzepatide combinations
Outcome group
Appetite and food intake · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Daily co-administration produces dose-dependent reductions in body weight and food intake that exceed both equimolar monotherapies and matched-dose comparator combinations incorporating semaglutide or tirzepatide.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we demonstrate enhanced metabolic benefits of a combination therapy with retatrutide, a unimolecular GLP-1R/GIPR/GCGR tri-agonist, and cagrilintide, an AMLNR/CALCR co-agonist, in diet-induced obese male rats.
Report a problemFND-4274490803
04AnimalAnimal study (in vivo)Efficacy outcome
In diet-induced obese male rats, daily co-administration of retatrutide and cagrilintide produced dose-dependent reductions in food intake that exceeded equimolar monotherapies and matched-dose semaglutide or tirzepatide combinations.
In plain wordsIn obese male rats, retatrutide plus cagrilintide reduced food intake more than either drug alone or semaglutide or tirzepatide combinations.
Peptide
Retatrutide
Outcome
DecreaseFood intake
Study
ratn: not reported in source
Diet-induced obese male rats
Comparator
Equimolar monotherapies and matched-dose semaglutide or tirzepatide combinations
Outcome group
Appetite and food intake · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Daily co-administration produces dose-dependent reductions in body weight and food intake that exceed both equimolar monotherapies and matched-dose comparator combinations incorporating semaglutide or tirzepatide.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we demonstrate enhanced metabolic benefits of a combination therapy with retatrutide, a unimolecular GLP-1R/GIPR/GCGR tri-agonist, and cagrilintide, an AMLNR/CALCR co-agonist, in diet-induced obese male rats.
Report a problemFND-4274490804

Studies that did not test the peptide alone12

In this study, the peptide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking the peptide.

05AnimalNot a test of Cagrilintide aloneAnimal study (in vivo)Efficacy outcome
In diet-induced obese male rats, the cagrilintide and retatrutide combination improved circulating cholesterol.
In plain wordsIn obese male rats, cagrilintide plus retatrutide improved blood cholesterol.
Peptide
Cagrilintide
Outcome
Direction not reportedCirculating cholesterol
Study
ratn: not reported in source
Diet-induced obese male rats
Outcome group
Lipids · Metabolic and weight
Source sentences
Summary
The combination therapy also improves circulating markers of metabolic health, including cholesterol, triglycerides and insulin levels.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we demonstrate enhanced metabolic benefits of a combination therapy with retatrutide, a unimolecular GLP-1R/GIPR/GCGR tri-agonist, and cagrilintide, an AMLNR/CALCR co-agonist, in diet-induced obese male rats.
In this study, Cagrilintide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Cagrilintide.
Report a problemFND-4274490805
06AnimalNot a test of Retatrutide aloneAnimal study (in vivo)Efficacy outcome
In diet-induced obese male rats, the retatrutide and cagrilintide combination improved circulating cholesterol.
In plain wordsIn obese male rats, retatrutide plus cagrilintide improved blood cholesterol.
Peptide
Retatrutide
Outcome
Direction not reportedCirculating cholesterol
Study
ratn: not reported in source
Diet-induced obese male rats
Outcome group
Lipids · Metabolic and weight
Source sentences
Summary
The combination therapy also improves circulating markers of metabolic health, including cholesterol, triglycerides and insulin levels.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we demonstrate enhanced metabolic benefits of a combination therapy with retatrutide, a unimolecular GLP-1R/GIPR/GCGR tri-agonist, and cagrilintide, an AMLNR/CALCR co-agonist, in diet-induced obese male rats.
In this study, Retatrutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Retatrutide.
Report a problemFND-4274490806
07AnimalNot a test of Cagrilintide aloneAnimal study (in vivo)Efficacy outcome
In diet-induced obese male rats, the cagrilintide and retatrutide combination improved circulating triglycerides.
In plain wordsIn obese male rats, cagrilintide plus retatrutide improved blood triglycerides.
Peptide
Cagrilintide
Outcome
Direction not reportedCirculating triglycerides
Study
ratn: not reported in source
Diet-induced obese male rats
Outcome group
Lipids · Metabolic and weight
Source sentences
Summary
The combination therapy also improves circulating markers of metabolic health, including cholesterol, triglycerides and insulin levels.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we demonstrate enhanced metabolic benefits of a combination therapy with retatrutide, a unimolecular GLP-1R/GIPR/GCGR tri-agonist, and cagrilintide, an AMLNR/CALCR co-agonist, in diet-induced obese male rats.
In this study, Cagrilintide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Cagrilintide.
Report a problemFND-4274490807
08AnimalNot a test of Retatrutide aloneAnimal study (in vivo)Efficacy outcome
In diet-induced obese male rats, the retatrutide and cagrilintide combination improved circulating triglycerides.
In plain wordsIn obese male rats, retatrutide plus cagrilintide improved blood triglycerides.
Peptide
Retatrutide
Outcome
Direction not reportedCirculating triglycerides
Study
ratn: not reported in source
Diet-induced obese male rats
Outcome group
Lipids · Metabolic and weight
Source sentences
Summary
The combination therapy also improves circulating markers of metabolic health, including cholesterol, triglycerides and insulin levels.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we demonstrate enhanced metabolic benefits of a combination therapy with retatrutide, a unimolecular GLP-1R/GIPR/GCGR tri-agonist, and cagrilintide, an AMLNR/CALCR co-agonist, in diet-induced obese male rats.
In this study, Retatrutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Retatrutide.
Report a problemFND-4274490808
09AnimalNot a test of Cagrilintide aloneAnimal study (in vivo)Efficacy outcome
In diet-induced obese male rats, the cagrilintide and retatrutide combination improved circulating insulin levels.
In plain wordsIn obese male rats, cagrilintide plus retatrutide improved blood insulin levels.
Peptide
Cagrilintide
Outcome
Direction not reportedCirculating insulin
Study
ratn: not reported in source
Diet-induced obese male rats
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
The combination therapy also improves circulating markers of metabolic health, including cholesterol, triglycerides and insulin levels.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we demonstrate enhanced metabolic benefits of a combination therapy with retatrutide, a unimolecular GLP-1R/GIPR/GCGR tri-agonist, and cagrilintide, an AMLNR/CALCR co-agonist, in diet-induced obese male rats.
In this study, Cagrilintide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Cagrilintide.
Report a problemFND-4274490809
10AnimalNot a test of Retatrutide aloneAnimal study (in vivo)Efficacy outcome
In diet-induced obese male rats, the retatrutide and cagrilintide combination improved circulating insulin levels.
In plain wordsIn obese male rats, retatrutide plus cagrilintide improved blood insulin levels.
Peptide
Retatrutide
Outcome
Direction not reportedCirculating insulin
Study
ratn: not reported in source
Diet-induced obese male rats
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
The combination therapy also improves circulating markers of metabolic health, including cholesterol, triglycerides and insulin levels.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we demonstrate enhanced metabolic benefits of a combination therapy with retatrutide, a unimolecular GLP-1R/GIPR/GCGR tri-agonist, and cagrilintide, an AMLNR/CALCR co-agonist, in diet-induced obese male rats.
In this study, Retatrutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Retatrutide.
Report a problemFND-4274490810
11AnimalNot a test of Cagrilintide aloneAnimal study (in vivo)Mechanism
In pair-feeding and weight-matching studies in rats, the enhanced weight loss with the cagrilintide and retatrutide combination was not explained by reduced food intake alone.
In plain wordsIn rats, the extra weight loss from cagrilintide plus retatrutide was not explained by eating less alone.
Peptide
Cagrilintide
Outcome
Not applicableWeight loss versus food intake (pair-feeding)
Study
ratn: not reported in source
Diet-induced obese male rats
Outcome group
Body weight · Metabolic and weight
Source sentences
Summary
Pair-feeding and weight-matching studies reveal that the enhanced weight loss cannot be explained by reduced food intake alone and enable discrimination between weight-loss-dependent and drug-specific molecular responses.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we demonstrate enhanced metabolic benefits of a combination therapy with retatrutide, a unimolecular GLP-1R/GIPR/GCGR tri-agonist, and cagrilintide, an AMLNR/CALCR co-agonist, in diet-induced obese male rats.
In this study, Cagrilintide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Cagrilintide.
Report a problemFND-4274490811
12AnimalNot a test of Retatrutide aloneAnimal study (in vivo)Mechanism
In pair-feeding and weight-matching studies in rats, the enhanced weight loss with the retatrutide and cagrilintide combination was not explained by reduced food intake alone.
In plain wordsIn rats, the extra weight loss from retatrutide plus cagrilintide was not explained by eating less alone.
Peptide
Retatrutide
Outcome
Not applicableWeight loss versus food intake (pair-feeding)
Study
ratn: not reported in source
Diet-induced obese male rats
Outcome group
Body weight · Metabolic and weight
Source sentences
Summary
Pair-feeding and weight-matching studies reveal that the enhanced weight loss cannot be explained by reduced food intake alone and enable discrimination between weight-loss-dependent and drug-specific molecular responses.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we demonstrate enhanced metabolic benefits of a combination therapy with retatrutide, a unimolecular GLP-1R/GIPR/GCGR tri-agonist, and cagrilintide, an AMLNR/CALCR co-agonist, in diet-induced obese male rats.
In this study, Retatrutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Retatrutide.
Report a problemFND-4274490812
13AnimalNot a test of Cagrilintide aloneAnimal study (in vivo)Mechanism
In rats, plasma proteomic profiling showed enrichment of bioenergetic processes with the cagrilintide and retatrutide combination.
In plain wordsIn rats, blood protein profiles showed more energy-related processes with cagrilintide plus retatrutide.
Peptide
Cagrilintide
Outcome
IncreasePlasma proteomic profile
Study
ratn: not reported in source
Diet-induced obese male rats
Outcome group
Mitochondrial function · Metabolic and weight
Source sentences
Summary
Plasma proteomic profiling highlights enrichment of bioenergetic processes with the combination therapy
1 context sentence(design, population, supporting numbers)
Summary · context
Here we demonstrate enhanced metabolic benefits of a combination therapy with retatrutide, a unimolecular GLP-1R/GIPR/GCGR tri-agonist, and cagrilintide, an AMLNR/CALCR co-agonist, in diet-induced obese male rats.
In this study, Cagrilintide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Cagrilintide.
Report a problemFND-4274490813
14AnimalNot a test of Retatrutide aloneAnimal study (in vivo)Mechanism
In rats, plasma proteomic profiling showed enrichment of bioenergetic processes with the retatrutide and cagrilintide combination.
In plain wordsIn rats, blood protein profiles showed more energy-related processes with retatrutide plus cagrilintide.
Peptide
Retatrutide
Outcome
IncreasePlasma proteomic profile
Study
ratn: not reported in source
Diet-induced obese male rats
Outcome group
Mitochondrial function · Metabolic and weight
Source sentences
Summary
Plasma proteomic profiling highlights enrichment of bioenergetic processes with the combination therapy
1 context sentence(design, population, supporting numbers)
Summary · context
Here we demonstrate enhanced metabolic benefits of a combination therapy with retatrutide, a unimolecular GLP-1R/GIPR/GCGR tri-agonist, and cagrilintide, an AMLNR/CALCR co-agonist, in diet-induced obese male rats.
In this study, Retatrutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Retatrutide.
Report a problemFND-4274490814
15AnimalNot a test of Cagrilintide aloneAnimal study (in vivo)Mechanism
In rats, brain transcriptomic profiling identified convergent central neuronal programmes linked to energy balance regulation with the cagrilintide and retatrutide combination.
In plain wordsIn rats, brain gene activity studies found shared nerve-cell programmes linked to energy balance with cagrilintide plus retatrutide.
Peptide
Cagrilintide
Outcome
Not applicableBrain transcriptomic profile
Study
ratn: not reported in source
Diet-induced obese male rats
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
whereas brain transcriptomic profiling identifies convergent central neuronal programmes linked to energy balance regulation.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we demonstrate enhanced metabolic benefits of a combination therapy with retatrutide, a unimolecular GLP-1R/GIPR/GCGR tri-agonist, and cagrilintide, an AMLNR/CALCR co-agonist, in diet-induced obese male rats.
In this study, Cagrilintide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Cagrilintide.
Report a problemFND-4274490815
16AnimalNot a test of Retatrutide aloneAnimal study (in vivo)Mechanism
In rats, brain transcriptomic profiling identified convergent central neuronal programmes linked to energy balance regulation with the retatrutide and cagrilintide combination.
In plain wordsIn rats, brain gene activity studies found shared nerve-cell programmes linked to energy balance with retatrutide plus cagrilintide.
Peptide
Retatrutide
Outcome
Not applicableBrain transcriptomic profile
Study
ratn: not reported in source
Diet-induced obese male rats
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
whereas brain transcriptomic profiling identifies convergent central neuronal programmes linked to energy balance regulation.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we demonstrate enhanced metabolic benefits of a combination therapy with retatrutide, a unimolecular GLP-1R/GIPR/GCGR tri-agonist, and cagrilintide, an AMLNR/CALCR co-agonist, in diet-induced obese male rats.
In this study, Retatrutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Retatrutide.
Report a problemFND-4274490816

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.

Versions 5 to 40Current
28 Oct 2026, 02:04 UTC
The same notice was added 36 times, first on 9 Oct 2026, 18:17 UTC. The status did not change between them.
Study results updated
Versions 2 to 4
9 Oct 2026, 03:07 UTC
The same notice was added 3 times, first on 9 Oct 2026, 03:04 UTC. The status did not change between them.
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:04 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

Journal Article

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