REDEFINE 1 试验中 CagriSema 剂量减少的特征分析.pdf

1、PO4.256Aim To characterise CagriSema dose reductions in the REDEFINE 1study to improve understanding of their timing and associatedclinical factors.Introduction In the REDEFINE 1 trial,treatment with once-weekly subcutaneous(s.c.)cagrilintide 2.4 mg and semaglutide 2.4 mg(CagriSema2.4 mg/2.4 mg)for

2、68 weeks resulted in weight loss of 22.7%compared with 2.3%with placebo in adults with overweight orobesity,and without diabetes(trial product estimand).1 The design of the REDEFINE 1 trial permitted the dose ofCagriSema to be reduced at investigator discretion.For thisreason,not all participants ra

3、ndomised to CagriSema completedthe trial on the maximum dose.Methods In the phase 3a REDEFINE 1 trial(NCT05567796),3417 adultswith a body mass index(BMI)30 kg/m2 or 27 kg/m2 with1 obesity-related complication were randomised to once-weeklys.c.CagriSema(n=2108),semaglutide(n=302),cagrilintide(n=302)o

4、r placebo(n=705),plus lifestyle intervention,for 68 weeks.CagriSema was initiated at a dose of 0.25 mg/0.25 mg andplanned to increase every 4 weeks until the maximum dose of2.4 mg/2.4 mg was reached at week 16,followed by a 52-weekmaintenance period(Figure 1).Investigators were permitted to delay do

5、se escalation or reducethe dose if the current dose was associated with adverse eventsor if the participant reached a BMI in the lower normal range andhad a health concern.Participants who were unable to reach the target maintenancedose were permitted to continue on the maximum tolerated dose.This a

6、nalysis characterised CagriSema dose reductions in relationto treatment duration,weight loss,BMI,and gastrointestinaladverse events(GI AEs).Figure 1.REDEFINE 1 trial design1Dose escalationMaintenance periodCagriSema 2.4 mg/2.4 mg(n=2108)Semaglutide 2.4 mg(n=302)Cagrilintide 2.4 mg(n=302)Placebo(n=70