On 5 June, at the 86th Scientific Sessions of the American Diabetes Association (ADA) in New Orleans, Louisiana, findings were presented on the effects of Novo Nordisk’s CagriSema on appetite, eating behaviour, and functional brain activity in adults with overweight or obesity. While GLP-1 receptor agonists have established robust efficacy in weight management, the neurobiological mechanisms underpinning appetite suppression with next-generation dual-mechanism therapies remain incompletely characterised. This study aimed to fill that gap, employing validated psychometric instruments and blood-oxygen-level-dependent functional MRI (BOLD fMRI) to quantify both subjective and objective changes in appetite and food cue responses.
CagriSema is a fixed-dose, once-weekly subcutaneous co-formulation of cagrilintide and semaglutide, acting as a Calcitonin Receptor (CALCR) agonist, GLP-1 receptor agonist (GLP-1RA), and Receptor Activity-Modifying Protein (RAMP) 1, 2, and 3 activator. It is currently under FDA review following a new drug application (NDA) submission in December 2025 for obesity and overweight, is in Phase III investigation globally for obesity, overweight, and type 2 diabetes (T2D), and is under Phase II evaluation for metabolic dysfunction-associated steatohepatitis (MASH) and diabetic peripheral neuropathy.
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In this study, 113 adults with a BMI ≥27 kg/m² were randomised to once-weekly subcutaneous CagriSema 2.4mg / 2.4mg or placebo for 54 weeks; the data reported at ADA 2026 reflected 22 weeks of treatment exposure (CagriSema n=54, placebo n=59). Endpoints assessed at baseline and week 22 included: mean postprandial appetite scores via Visual Analog Scale (VAS); body weight; ad libitum energy intake across lunch, dinner, and a snack box; validated eating behaviour questionnaires (Control of Eating Questionnaire [CoEQ], Power of Food [PoF], and DAILY EATS); and differential brain activation in response to high-calorie food cues assessed by BOLD fMRI.
In results presented by Novo Nordisk’s Janne Rasmus Hingst, CagriSema produced a statistically significant and clinically meaningful reduction in postprandial appetite versus placebo: mean VAS scores declined by −24.19mm with CagriSema versus −7.29mm with placebo, yielding an estimated treatment difference of −16.91mm (p<0.0001). CagriSema also reduced body weight and energy intake, with improvements across CoEQ, PoF, and DAILY EATS scores collectively reflecting a substantially reduced drive to eat. At the neural level, fMRI revealed differential activation patterns between arms: CagriSema elicited greater activation in the mediodorsal thalamus and putamen, regions implicated in sensory integration and reward-based motivation; activation in the postcentral gyrus decreased, which is associated with somatosensory food perception.
These findings provide mechanistic granularity beyond weight and metabolic endpoints, demonstrating that CagriSema modulates central circuits governing satiety signalling, hunger, and hedonic drive. The engagement of thalamic and striatal regions indicates a dual peripheral-central mode of action that may meaningfully differentiate CagriSema from GLP-1 monotherapy.
Key opinion leaders interviewed by GlobalData anticipate CagriSema’s potential to “cannibalise the Semaglutide market”, adding that “it has weight loss similar to Tirzepatide”.
As CagriSema approaches potential regulatory approval, characterisation of its neurobiological footprint strengthens the mechanistic rationale for its efficacy ceiling and supports its competitive positioning in an increasingly crowded obesity pharmacotherapy landscape. According to GlobalData’s Pharma Intelligence Center, there are 46 Phase III candidates, 109 Phase II candidates, and 165 Phase I candidates for overweight and obesity globally.
