Zenagamtide 是一种新型长效单分子 GLP-1 和胰淀素受体激动剂不影响复方口服避孕药左炔诺孕酮 炔雌醇的药代动力学.pdf

1、 PO4.218Aim To evaluate the effect of co-administration of oral or subcutaneous(s.c.)zenagamtide on the pharmacokinetics(PK)of a combined oral contraceptive(OC)pill.Introduction Glucagon-like peptide-1(GLP-1)receptor agonists have demonstrated clinically significant reductions in body weight,and add

2、itional benefits including reductions in cardiovascular risk and improvements in outcomes in people with heart failure,chronic kidney disease and metabolic dysfunction-associated steatohepatitis.15 Amylin,a peptide hormone co-secreted with insulin,regulates body weight by reducing appetite and energ

3、y intake,and increasing satiety through the activation of the amylin receptor.6 Zenagamtide,previously known as amycretin(NNC0487-0111),is a novel,long-acting,unimolecular GLP-1,amylin and calcitonin receptor agonist with oral and s.c.formulations under development for weight management and type 2 d

4、iabetes treatment.7,8 A previous preclinical study showed that zenagamtide activates GLP-1,amylin and calcitonin receptors in human,mouse and rat cell-based systems,and targets areas of the mouse brain that regulate food intake.9 In a previous phase 1 study in participants with overweight or obesity

5、,once-daily oral zenagamtide(up to 250 mg)led to a mean reduction in body weight of up to 13.1%at 12 weeks,compared with 1.2%with placebo with no weight loss plateau.7 In a phase 1b/2a study,once-weekly s.c.zenagamtide(up to 60 mg)led to significant reductions in body weight of up to 24.3%,compared

6、with 1.1%with placebo with no signs of weight loss reaching a nadir after 36 weeks of treatment.8 In both studies,zenagamtide appeared safe and tolerable in participants with overweight or obesity in line with the GLP-1 and amylin receptor agonist classes.7,8Methods In this single-centre,one-sequenc