Continued CagriSema treatment preserves weight loss by reducing energy intake and maintaining energy expenditure in rats
- Design
- Animal study · Intermediate outcome
- Match to healthy normal-weight adults aged 55–75
- Not human evidenceVERY_INDIRECT: the subjects are male diet-induced obese rats, not people.
- Could weight loss explain it?
- Not applicableThe outcomes are body weight, energy intake and energy expenditure themselves, so mediation by weight loss does not arise. The design did include weight-matched and pair-fed calorie-restricted comparison groups, which is why the split of 86% intake and 14% expenditure can be reported.
- Study tier
- Study tier 4VERY_LOW: a preclinical study in rats, the model's lowest tier, reporting no group sizes, doses, confidence intervals or p values.
- Assessment
- Version 3 · Two independent AI reviews agreed · Nov 6, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
Male diet-induced obese rats received CagriSema, the amylin agonist cagrilintide combined with semaglutide, for 6 weeks and were followed for 4 weeks after it stopped, alongside a vehicle group, a calorie-restricted group matched to the drug's weight loss and a pair-fed group matched to its food intake. Lower food intake accounted for 86% of the drug's weight-loss effect and preserved energy expenditure for 14%, whereas the weight-matched calorie-restricted rats showed the expected fall in energy expenditure. Stopping treatment brought overeating and rapid weight regain, with the metabolic adaptation reversing within about 7 days. This is an animal study with no group sizes reported, and the GLP-1 drug was given only as part of the combination.
01Findings
What the study reported
- Drugs
- Semaglutide
- Treatment duration
- 6 weeks
- Comparator
- vehicle, calorie restriction weight-matched to CagriSema weight loss, and pair-feeding matched to CagriSema food intake
- Primary outcome
- energy balance (energy intake and energy expenditure) during treatment, weight maintenance and after discontinuation
- Effect
- Reduced energy intake and preserved total energy expenditure explained 86% and 14% of CagriSema weight-loss efficacy; energy expenditure was significantly lower in the weight-matched calorie-restricted rats; stopping treatment caused hyperphagia and rapid weight regain, with metabolic adaptation reversing within about 7 days
- 95% confidence interval
- not reported in abstract
- Follow-up
- 4 weeks after discontinuation
- Adverse events
- not reported in abstract
- Limitations
- A preclinical experiment in male diet-induced obese rats only, with no group sizes, doses, confidence intervals or p values reported, measuring energy balance rather than clinical outcomes; the drug was given only as the cagrilintide-semaglutide combination, so the GLP-1 component's own contribution cannot be separated.
Who was studied
- Sex distribution
- all male
- Obesity status
- obesity required (male diet-induced obese rats)
- Diabetes status
- not reported in abstract
- Cvd status
- not reported in abstract
- Ckd status
- not reported in abstract
- Baseline condition
- diet-induced obesity in male rats
- Inclusion exclusion
- male diet-induced obese rats allocated to vehicle, CagriSema, weight-matched calorie restriction or pair-feeding
Study quality details
- Study design
- Preclinical (animal)
- Sample size
- not extracted
- Randomization
- not reported in abstract
- Blinding
- not stated
- Comparator
- vehicle, calorie restriction weight-matched to CagriSema weight loss, and pair-feeding matched to CagriSema food intake
- Follow up duration
- 4 weeks after discontinuation
- Outcome type
- intermediate
- Replication
- not assessed
- Consistency with other evidence
- not assessed
- Population applicability
- VERY_INDIRECT
- Statistical precision
- no confidence intervals, p values or group sizes reported; one difference described as significant
- Risk of bias
- not assessed
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- not reported in abstract
- Industry funded
- Unclear
- Manufacturer
- not stated in source
- Sponsor role
- not reported in abstract
- Author conflicts
- Named authors are employed by Novo Nordisk A/S and are minor shareholders, one of them also reporting that employment relationship; any other authors declare no competing interests.
- Independent replication
- unknown
- Notes
- Authors declare relationships with the drug's manufacturer: Novo Nordisk A/S (employment, minor shareholdings)
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[PURPOSE] CagriSema (CS), combining the amylin receptor agonist cagrilintide with the glucagon-like peptide 1 receptor agonist semaglutide, is being developed for obesity and type 2 diabetes. We quantified CS effects on energy balance during initial treatment, weight maintenance, and after discontinuation. [METHODS] Male diet-induced obese rats underwent indirect calorimetry during 6 weeks of treatment and for 4 weeks after discontinuation. Treatments were a) vehicle, b) CS, c) calorie-restriction to match CS body weight loss (weight matched, WM), and d) calorie-restriction to match CS food intake (pair-feeding, PF). [RESULTS] CS effects occurred in four phases. During days 1-10 (Phase I), CS induced rapid weight loss mainly through reduced energy intake (EI), while energy expenditure (EE) was relatively preserved. EE was significantly lower in WM rats, consistent with metabolic adaptation. During days 11-42 (Phase II), reduced body weight was maintained in the CS, WM, and PF groups, and respiratory exchange ratio converged across groups, indicating metabolic steady state had been reached. Reduced EI and preserved total EE respectively explained 86% and 14% of CS weight loss efficacy. Maintained resting/sleeping EE contributed to the total EE preservation. Treatment discontinuation (days 43-52, Phase III) caused hyperphagia and rapid weight regain. During days 53-68 (Phase IV), all groups reached metabolic steady state and weight gain returned to pretreatment rates. Body weight plateaued in approximately half the time needed to reach metabolic steady state, and metabolic adaptation reversed within ∼7 days after discontinuation. [CONCLUSIONS] By persistently lowering EI and attenuating metabolic adaptation, CS enables sustained weight loss in rats; however, the reversal after treatment cessation suggests that chronic pharmacological therapy may be required to maintain weight loss.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Nov 1, 2026 | 42951207 first ingestion |
| owner-review | Nov 6, 2026 | reviewed_by set to Carrie Schluter (2026-11-05) on the owner's own confirmation. The assessment is unchanged and still the auto-classifier's, so its extracted values stay withheld under the 2026-10-18 decision. |
| reextract | Nov 6, 2026 | industry_funded: 'unclear' -> 'yes'; sponsor_role: 'not reported in abstract' -> 'manufacturer funded the study (sponsor role in design/analysis not stated in abstract)'; funding_source: 'not reported in abstract' -> 'Novo Nordisk (named in the conflicts statement)'; evidence_components.funding_conflicts: 'unclear' -> 'yes'. Q-043: manufacturer, drug_details.dose and the funding fields re-extracted by auto-classifier-v1.2. manufacturer no longer reads companies named only in the authors' conflicts statement (IN-062) and refuses a multi-company roster; dose is tied to the GLP-1 agent by name, never reads a concentration, records a multi-dose design whole and keeps a frequency written beside the amount; industry_funded, sponsor_role and funding_source read the conflicts statement's own sponsor sentences, a supplier counting as partial. Every other value is carried forward unchanged, evidence_level included. Owner decisions IN-064, 2026-11-06. |
| pubmed | Nov 8, 2026 | 42951207 duplicate matched on doi |