Aims: In this post-hoc analysis, we investigated the baseline characteristics (week-0) and change in weight and waist circumference at the end of the open-label lead-in period (week-36) associated with varying degrees of weight regain after tirzepatide withdrawal.
Methods: SURMOUNT-4 participants who achieved ≥10% weight reduction with 36-weeks of tirzepatide treatment (maximally tolerated dose (MTD) of 10 or 15mg) and randomized to placebo (N=308) were included in this post-hoc analysis. Participants’ baseline characteristics and change in weight and waist circumference were calculated descriptively by the degree of weight regain, from Week 36-88, as a percentage of weight reduction, from Week 0-36.
Results: Participants in the lower weight regain groups exhibited significantly greater mean reductions in weight (%) from the start of the lead-in period to randomization; -23.6%, -23.4%, -22.6% and -18.3% in the <25%, ≥25-<50%, ≥50-<75% and ≥75% groups (p<.001). Greater reduction in mean waist circumference (cm) from the start of the lead-in period to randomization was also observed in participants with lower weight regain; -19.6cm, -20.0cm, -17.9cm and –16.2cm in the <25%, ≥25-<50%, ≥50-<75% and ≥75% groups (p=.022).
Participants had no significant differences across weight regain groups in demographic or baseline clinical characteristics.
Conclusion: In this post-hoc analysis of participants who were withdrawn from treatment with tirzepatide in the SURMOUNT-4 clinical trial, participants with less body weight regain demonstrated greater reductions in body weight and waist circumference during the initial open-label lead-in period. There were no significant differences in baseline demographic or clinical characteristics across groups with different degrees of weight regain. These findings are consistent with the multifactorial and complex nature of obesity.