1035-OR: Effects of CagriSema on Appetite and Functional Brain Activity in People with Overweight/Obesity

Introduction and Objective: CagriSema (fixed-dose combination of semaglutide 2.4 mg and cagrilintide 2.4 mg) is currently under development for weight management and type 2 diabetes. This clinical pharmacology study aimed to investigate the CagriSema effects on appetite, eating behavior, and brain responses to food cues in people with overweight/obesity. Methods: Adults with BMI ≥27 kg/m2 were randomized to once-weekly s.c. CagriSema 2.4 mg/2.4 mg or placebo for 54 weeks; results after 22 weeks of treatment exposure are reported here. Endpoints assessed at baseline and after 22 weeks’ treatment included: mean postprandial appetite scores (Visual Analog Scale [VAS]); body weight; energy intake of ad libitum lunch, dinner, and snack box; Control of Eating Questionnaire (CoEQ), Power of Food (PoF) and DAILY EATS questionnaires; and brain responses to food cues using blood-oxygen-level-dependent functional MRI (fMRI). Safety was also assessed. Results: In total, 113 adults were exposed to 22 weeks of treatment (CagriSema n=54, placebo n=59). Changes [95% CI] from baseline in mean postprandial appetite VAS scores were -24.19 mm [-28.50;-19.89] (CagriSema) and -7.29 mm [-11.40;-3.17] (placebo); estimated treatment difference [95% CI]: -16.91 mm [-22.92;-10.89], p<0.0001. CagriSema vs placebo reduced body weight and energy intake and improved CoEQ, PoF and DAILY EATS questionnaire scores, indicating reduced drive to eat. Differential brain activation in response to high-calorie food cues was detected between CagriSema and placebo after 22 weeks of treatment vs baseline: CagriSema showed greater activation in the mediodorsal thalamus and putamen and decreased activation in the postcentral gyrus vs placebo. There were no unexpected safety findings. Conclusion: CagriSema improved appetite and eating control vs placebo in people with overweight/obesity. CagriSema treatment-related effects on neural responses as characterized by fMRI suggest modulation of brain regions implicated in satiety, hunger, and motivation. Disclosure N. Bak: Employee; Ended; Lundbeck. Stock/Shareholder; Current; Novo Nordisk, Lilly. M. Alex: None. S.A. Fuglsang: Stock/Shareholder; Current; Novo Nordisk A/S. Employee; Current; Novo Nordisk A/S. C. Broholm: Employee; Current; Novo Nordisk. C. Keicher: None. R. Setton: Other - I have a relationship with Perceptive (CRO) as a vendor for Novo Nordisk.; Current; Perceptive. E. Sikoglu: None. E.W. Lehmann: Employee; Current; Novo Nordisk. J.R. Hingst: Employee; Current; Novo Nordisk. Stock/Shareholder; Current; Novo Nordisk. Funding Novo Nordisk A/S is the sponsor of this study and its related publication.