CagriSema rat study reports weight loss driven mainly by reduced energy intake, regain after stopping
In male diet-induced obese rats, indirect calorimetry over 6 weeks of CagriSema treatment and 4 weeks after discontinuation showed weight loss attributed mainly to lower energy intake, with rapid regain once treatment stopped.
Molecular metabolism · 2026 · Animal · Rat · Published October 29, 2026
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What the study did
This was an animal study in rats; the abstract does not state how many animals were used. Male diet-induced obese rats underwent indirect calorimetry during 6 weeks of treatment and for 4 weeks after discontinuation, according to the methods section of the abstract.
The authors compared four conditions: vehicle, CagriSema (described as combining the amylin receptor agonist cagrilintide with the glucagon-like peptide 1 receptor agonist semaglutide), calorie restriction matched to CagriSema body weight loss (weight matched), and calorie restriction matched to CagriSema food intake (pair-feeding). The abstract does not report the dose, route, or dosing frequency used in the animals.
What it reported
The authors describe four phases. During days 1-10 (Phase I), the abstract states that CagriSema induced rapid weight loss mainly through reduced energy intake, while energy expenditure was relatively preserved, and that energy expenditure was significantly lower in weight-matched rats, which the authors interpret as metabolic adaptation.
During days 11-42 (Phase II), reduced body weight was maintained in the CagriSema, weight-matched, and pair-fed groups, and the respiratory exchange ratio converged across groups. The authors report that reduced energy intake and preserved total energy expenditure respectively explained 86% and 14% of CagriSema weight loss efficacy in this rat model.
After discontinuation (days 43-52, Phase III), the abstract reports hyperphagia and rapid weight regain, and during days 53-68 (Phase IV) weight gain returned to pretreatment rates. The authors state that metabolic adaptation reversed within approximately 7 days after discontinuation.
Limitations
This work was conducted in male diet-induced obese rats only, so the findings are laboratory animal results and do not describe outcomes in people. The abstract does not report the number of animals per group, nor the dose, route, or schedule of the treatments given.
The comparison groups were calorie-restriction conditions rather than an alternative drug, and the abstract reports only group-level energy balance measures over a 68-day window. The authors' own concluding sentence frames the post-treatment reversal as suggesting that chronic pharmacological therapy may be required to maintain weight loss, which is an inference from this rat model rather than a clinical finding.
Regulatory context
Cagrilintide, studied here in the coformulation referred to as CagriSema, is not an FDA-approved drug for any use. This status comes from the site's regulatory review and not from the study described on this page.
Claims and where they come from
Each statement below is followed by the passage of the source record it was checked against.
The study used male diet-induced obese rats monitored by indirect calorimetry for 6 weeks of treatment and 4 weeks after stopping.
“Male diet-induced obese rats underwent indirect calorimetry during 6 weeks of treatment and for 4 weeks after discontinuation.”
In the early phase, the authors attribute rapid weight loss mainly to reduced energy intake, with energy expenditure relatively preserved.
“During days 1-10 (Phase I), CS induced rapid weight loss mainly through reduced energy intake (EI), while energy expenditure (EE) was relatively preserved.”
Calorie-restricted weight-matched rats showed significantly lower energy expenditure, which the authors describe as metabolic adaptation.
“EE was significantly lower in WM rats, consistent with metabolic adaptation.”
The authors quantify the contributions to weight loss efficacy as 86% from reduced energy intake and 14% from preserved total energy expenditure.
“Reduced EI and preserved total EE respectively explained 86% and 14% of CS weight loss efficacy.”
Stopping treatment was followed by hyperphagia and rapid weight regain in the rats.
“Treatment discontinuation (days 43-52, Phase III) caused hyperphagia and rapid weight regain.”
The authors conclude that the reversal after cessation suggests chronic pharmacological therapy may be needed to maintain weight loss.
“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.”
Common questions
Does the abstract state what dose of CagriSema the rats received?
No. The abstract names the treatment groups (vehicle, CagriSema, weight-matched calorie restriction, and pair-feeding) but does not report a dose, route, or dosing frequency.
Were there comparison groups?
Yes. The abstract describes vehicle-treated rats, a calorie-restriction group matched to CagriSema body weight loss, and a calorie-restriction group matched to CagriSema food intake.
What happened after treatment was stopped?
The abstract reports that discontinuation during days 43-52 caused hyperphagia and rapid weight regain, that weight gain returned to pretreatment rates during days 53-68, and that metabolic adaptation reversed within about 7 days after discontinuation.
Do these results apply to people?
The study was conducted in male diet-induced obese rats. The findings are animal results, and the abstract reports no human data.
Source
- 1.Continued CagriSema treatment preserves weight loss by reducing energy intake and maintaining energy expenditure in rats — Molecular metabolism (2026)AnimalratPMID 42951207DOI 10.1016/j.molmet.2026.102464