Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults with Obesity (SURMOUNT-4)

How does once-weekly subcutaneous tirzepatide affect maintenance of weight loss in individuals with obesity or overweight? Methods : SURMOUNT-4 is a phase 3, double-blind, 88-week study that investigates the maximum tolerated dose (MTD) of tirzepatide (10 mg or 15 mg QW), compared with placebo, on the maintenance of weight loss for 52 weeks after an initial 36-week open-label tirzepatide lead-in treatment period. In the study, participants without T2DM and with obesity (BMI ≥30 kg/m^2) or overweight (BMI ≥27 kg/m^2) with at least 1 weight-related comorbid condition were enrolled. The efficacy estimand was used to assess efficacy which represented the average treatment effect, prior to treatment discontinuation. Results : 803 participants enrolled in the lead-in period and 670 were randomized to continue tirzepatide MTD (N=335) or switch to placebo (N=335). For randomized participants, the mean weight loss was 20.9% following 36-week open-label treatment. SURMOUNT-4 met the primary endpoint. From week 36 to week 88, those taking tirzepatide had an additional weight change of -6.7%, while those taking placebo had a mean weight regain of 14.8%. The percentage of participants at 88 weeks who maintained ≥80% of the weight loss during the lead-in period was 93.4% with tirzepatide and 13.5% with placebo. In addition, participants who remained on tirzepatide achieved a total of 26.0% mean weight loss over the 88-week period. The most frequent adverse events with tirzepatide were gastrointestinal disorders, generally being mild to moderate in severity. Conclusion : In this 88-week trial in participants with obesity or overweight, withdrawing tirzepatide after 36 weeks treatment led to substantial regain of lost weight, whereas continued treatment maintained and augmented initial weight reduction. ^ denotes square root in this submission Publication History Article published online: 18 April 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany