The obesity pandemic is a major health crisis and current treatments are primarily focused on weight loss. However, health benefits from weight loss can be compromised by the weight-loss-associated loss of lean body mass. Here we investigate the effect of petrelintide, a novel once-weekly amylin analog on weight loss with comparison of changes of fat mass and lean mass in DIO (diet-induced obese) rats.
DIO rats 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) for a 30-day treatment period. Body weight was measured daily, and body composition was measured by use of EchoMRI at baseline and at day 29 of treatment.
Treatment with liraglutide and petrelintide resulted in significantly 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 fat mass in comparison to vehicle, which liraglutide did not (2.0% ± 0.5 liraglutide, -0.3 % ± 0.5 petrelintide 2 nmol/kg, -1.6 % ± 0.5 petrelintide 10 nmol/kg, 3.2 % ± 0.4 vehicle; mean change in fat mass as % of body weight ± SEM).
Furthermore, treatment with petrelintide resulted in significant preservation of relative lean mass in comparison to vehicle, which liraglutide did not (-3.8 % ± 0.3 vehicle, -2.4 % ± 0.6 liraglutide, -0.8 % ± 0.4 petrelintide 2 nmol/kg, 0.1 % ± 0.4 petrelintide 10 nmol/kg; mean change in lean mass as % of body weight ± SEM).
In conclusion, petrelintide shows preferential fat mass loss and preservation of relative lean mass during weight loss in DIO rats. Based on these findings, petrelintide could hold the potential to reduce the loss of lean body mass associated with weight loss in humans. Petrelintide is currently being explored in a multiple ascending dose (MAD) study to assess the potential for the management of obesity.
B. Vestergaard: Employee; Zealand Pharma A/S, Novo Nordisk A/S. T. Baader-Pagler: Employee; Boehringer-Ingelheim. J. Griffin: Employee; Zealand Pharma A/S.
