1661-P: Petrelintide (ZP8396) Selectively Reduces Intake of High-Fat Diet in DIO Rats

The obesity pandemic is a major health crisis and there is a need for effective pharmacotherapies. Overconsumption of highly palatable food is associated with obesity. Petrelintide, a novel once-weekly amylin analog currently in phase 1 clinical testing, induces meaningful reductions in body weight in lean and overweight subjects. Here we investigate the effect of petrelintide on food preference in DIO (diet-induced obese) rats to determine whether petrelintide holds the potential to address overconsumption of highly palatable food in humans.DIO rats were given ad libitum access to chow diet and high fat diet during a 30-day treatment period. Animals were treated with either vehicle (every second day), liraglutide (5 nmol/kg twice daily) or petrelintide (2 nmol/kg every second day or 10 nmol/kg every fourth day). Body weight, chow intake and high fat diet intake were measured daily.

Treatment with liraglutide and petrelintide resulted in significant lower relative body weight compared to vehicle (3.3 % ± 0.7 vehicle, -0.1 % ± 1.1 liraglutide, -4.1 % ±0.6 petrelintide 2 nmol/kg, -7.8 % ± 0.7 petrelintide 10 nmol/kg; relative to initial body weights ± SEM). Treatment with petrelintide resulted in significant reduction of total cumulative intake of high fat diet compared to vehicle, in contrast to liraglutide (834 g ± 31.1 vehicle, 796 g ± 25.6 liraglutide, 646 g ± 22.3 petrelintide 2 nmol/kg, 576 g ± 17.4 petrelintide 10 nmol/kg; g ± SEM). No change in total cumulative intake of chow was observed in any groups compared to vehicle.

In conclusion, petrelintide reduces food intake and body weight in DIO rats primarily by lowering intake of high fat diet. Based on these findings petrelintide might hold the potential to address overconsumption of highly palatable food in humans. Petrelintide is currently being explored in a multiple ascending dose (MAD) study to assess the potential for the management of obesity.