Cagrilintide plus retatrutide in diet-induced obese male rats reports greater weight loss than monotherapy
A preclinical study in diet-induced obese male rats reports that daily co-administration of the amylin analogue cagrilintide with the tri-agonist retatrutide lowered body weight and food intake more than either drug alone.
Nature metabolism · 2026 · Animal · Rat · Published October 11, 2026
This page reports what published studies found. It is not medical advice, no provider-patient relationship is created by reading it, and nothing here is a recommendation to use any compound. Talk with a licensed clinician about your own situation. Read the full disclaimer.
What the study did
This is an animal study conducted in diet-induced obese male rats; the abstract does not state how many animals were used, so the sample size is unknown. The authors tested daily co-administration of retatrutide, described as a unimolecular GLP-1R/GIPR/GCGR tri-agonist, together with cagrilintide, described as an AMLNR/CALCR co-agonist.
Comparisons included equimolar monotherapies and what the authors call matched-dose comparator combinations incorporating semaglutide or tirzepatide. The work also included pair-feeding and weight-matching studies, plasma proteomic profiling and brain transcriptomic profiling.
What it reported
The authors report that daily co-administration produced dose-dependent reductions in body weight and food intake that exceeded both the equimolar monotherapies and the matched-dose comparator combinations. They also report improvements in circulating markers of metabolic health, including cholesterol, triglycerides and insulin levels.
According to the abstract, pair-feeding and weight-matching experiments indicated that the enhanced weight loss could not be explained by reduced food intake alone, and allowed the authors to separate weight-loss-dependent from drug-specific molecular responses. Plasma proteomics highlighted enrichment of bioenergetic processes, while brain transcriptomics identified convergent central neuronal programmes linked to energy balance regulation.
Reported dosing
The abstract does not report any specific doses, concentrations or injection schedule beyond stating that administration was daily and that the body-weight and food-intake effects were dose-dependent. Because no numbers or units are given in the source text, no regimen is listed here, and nothing in this report describes an amount given to any species.
Limitations
These are preclinical findings in rats, and the authors themselves describe them as preclinical; results in animals do not establish what happens in people. Only male rats were studied, so the abstract reports nothing about female animals.
The abstract does not state the number of animals, the doses used, the duration of treatment, randomization or blinding, or who funded the work. Outcomes such as proteomic and transcriptomic enrichment are described in summary terms without effect sizes or statistical detail in the text provided.
Regulatory context
Cagrilintide, also referred to as AM833 or NNC0174-0833 and coformulated with semaglutide as CagriSema, is not an FDA-approved drug for any use. This status comes from the site's regulatory review rather than from this study.
Claims and where they come from
Each statement below is followed by the passage of the source record it was checked against.
The study was conducted in diet-induced obese male rats and tested a combination of retatrutide and cagrilintide.
“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”
The authors report dose-dependent reductions in body weight and food intake that exceeded monotherapies and comparator combinations.
“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.”
Circulating metabolic markers, including cholesterol, triglycerides and insulin, were reported to improve with the combination.
“The combination therapy also improves circulating markers of metabolic health, including cholesterol, triglycerides and insulin levels.”
Pair-feeding and weight-matching experiments indicated the added weight loss was not attributable to reduced food intake alone.
“Pair-feeding and weight-matching studies reveal that the enhanced weight loss cannot be explained by reduced food intake alone”
The authors describe the findings as preclinical and frame them as support for five-receptor polypharmacology in future drug design.
“our preclinical findings support five-receptor polypharmacology as a strategy for efficaciously lowering body weight and provide guidance for the design of next-generation unimolecular multi-receptor agonists”
Common questions
Were any doses reported in the abstract?
No. The abstract states that co-administration was daily and that effects were dose-dependent, but it does not give any specific amounts, units or treatment duration.
Was this study done in people?
No. The work was performed in diet-induced obese male rats, and the authors describe the results as preclinical findings.
What comparison groups were used?
The abstract states the combination was compared with equimolar monotherapies and with matched-dose comparator combinations incorporating semaglutide or tirzepatide.
How many animals were studied?
The abstract does not state the number of rats used, nor does it describe randomization or blinding.
Source
- 1.Cagrilintide and retatrutide combination therapy enhances weight loss and metabolic outcomes in obese male rats — Nature metabolism (2026)AnimalratPMID 42744908DOI 10.1038/s42255-026-01603-y