Semaglutide, a GLP-1 analogue, is being investigated in people with overweight or obesity. A post-hoc analysis of the STEP 4 trial aimed to identify whether early weight loss is predictive of later weight loss with maintenance once-weekly subcutaneous semaglutide 2.4 mg.
STEP 4 was a randomised, double-blind, phase 3 trial (NCT03548987). Adults with body mass index (BMI) ≥27 kg/m2 and ≥1 weight-related comorbidity or BMI ≥30 kg/m2, without type 2 diabetes, underwent a 20-week run-in. Participants reaching the maintenance dose of once-weekly subcutaneous semaglutide 2.4mg at week 20 were randomised 2:1 to semaglutide 2.4mg or placebo, as adjunct to lifestyle intervention, for 48 weeks. Percentage change in body weight from week 0-68 was estimated; trial product estimand results are presented. Participants with ≥5% weight loss at week 20 were considered responders. Whether the week 20 response to semaglutide predicted ≥5% weight loss by week 68 was also assessed.
803 of 902 participants who started STEP 4 were randomised at week 20 (semaglutide: n=535, placebo: n=268; mean age 46 years, body weight 107.2 kg, BMI 38.4 kg/m2; 79.0% female). For 88.0% of participants randomised to semaglutide who were week-20 responders, mean body weight change from week 0-68 was –19.7%. For non-responders at week 20, mean body weight change was –6.4% with continued semaglutide vs –0.3% with placebo. Of participants randomised to semaglutide, 86.2% achieved ≥5% weight loss at week 68. Being a responder at week 20 was highly predictive of achieving this outcome (positive predictive value: 96.4%).
In STEP 4, most participants randomised to once-weekly semaglutide 2.4 mg maintenance at week 20 lost ≥5% body weight by week 68, with many achieving this by week 20. Weight loss with semaglutide was greater among early responders, but non-responders also achieved clinically relevant weight loss by week 68 if semaglutide treatment was continued.