Poster Presentation ANZOS Annual Scientific Meeting 2021

Clinically relevant weight loss is achieved independently of early weight loss response to once-weekly subcutaneous semaglutide 2.4 mg (STEP 4) (#233)

Joseph Proietto 1 , Ofri Mosenzon 2 , Timothy Garvey 3 , Dan Hesse 4 , Anna Koroleva 5 , Robert F Kushner 6 , Soo Lim 7 , Ildiko Lingvay 8 , Signe Olrik Rytter Wallenstein 5 , Thomas A Wadden 9 , Carel W Le Roux 10
  1. University of Melbourne, Melbourne, Vic, Australia
  2. Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
  3. Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
  4. Novo Nordisk A/S, Søborg, Denmark
  5. Novo Nordisk A/S, Søborg, Denmark
  6. Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
  7. Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, , Seongnam, South Korea
  8. UT Southwestern Medical Center, Dallas, TX, USA
  9. Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
  10. Diabetes Complications Research Centre, Conway Institute, University College Dublin, Dublin, Ireland

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.