Introduction: This post hoc analysis of the STEP UP trial evaluated the effects of early response on overall weight reduction.
Methods: In the phase 3b STEP UP trial (NCT05646706), participants ≥18 years with body mass index (BMI) of ≥30 kg/m2 were randomised 5:1:1 to once-weekly subcutaneous semaglutide 7.2 mg 2.4 mg, or placebo for 72 weeks. Early responders (ERs) and responders (Rs) were defined post hoc as participants with ≥15% or <15% weight reduction by week 24, respectively. Proportions of ERs and Rs were described for the on-treatment period, with weight reduction trajectories from baseline to week 72 by study group and responder status.
Results: Of 1407 participants, 22.6% (n=318) were classified as ERs. Across all groups at baseline, ERs had a mean weight of 104.3–105.0 kg, mean BMI of 36.8–37.8 kg/m² and 78.6–83.3% were female. Rs had a mean weight of 112.7–119.7 kg, mean BMI of 39.8–41.2 kg/m² and 65.4–73.1% were female. Weight reduction trajectories were similar for ERs receiving semaglutide 7.2 mg or 2.4 mg, with estimated mean reductions at week 72 of 29.1 kg and 26.2 kg (27.7% and 24.8%), respectively. Rs receiving semaglutide 7.2 mg or 2.4 mg also achieved substantial weight reductions at week 72 (17.7 kg and 15.0 kg; 15.4% and 13.2%, respectively). There were no significant interactions between semaglutide dose and responder status for overall mean weight change (kg: p=0.888; %: p=0.647). Adverse events were reported by 91.1%, 92.9% and 66.7% of ERs, and 86.1%, 81.8%, and 77.9% of Rs receiving semaglutide 7.2 mg, semaglutide 2.4 mg and placebo, respectively.
Conclusion: In STEP UP, >20% of participants were classified as ERs. In both semaglutide groups, ERs and Rs achieved substantial weight reduction at week 72 supporting continued treatment in the absence of an early response.