Oral Presentation ANZOS Annual Scientific Meeting 2021

Weight loss maintenance with once-weekly semaglutide 2.4 mg in adults with overweight or obesity reaching maintenance dose (STEP 4) (#75)

Joseph Proietto 1 , Domenica M Rubino 2 , Niclas Abrahamsson 3 , Melanie Davies 4 , Dan Hesse 5 , Frank Greenway 6 , Camilla Jensen 7 , Ildiko Lingvay 8 , Ofri Mosenzon 9 , Julio Rosenstock 10 , Miguel A Rubio 11 , Gottfried Rudofsky 12 , Sayeh Tadayon 7 , Thomas Wadden 13 , Dror Dicker 14
  1. University of Melbourne, Melbourne, Vic, Australia
  2. Washington Center for Weight Management, Arlington, VA, USA
  3. Endocrinology Unit, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
  4. Diabetes Research Centre, University of Leicester and NIHR Leicester Biomedical Research Centre, Leicester General Hospital, Leicester, UK
  5. Novo Nordisk A/S, Søborg, Denmark
  6. Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA
  7. Novo Nordisk A/S, Søborg, Denmark
  8. UT Southwestern Medical Center, Dallas, TX, USA
  9. Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
  10. Dallas Diabetes Research Center at Medical City, Dallas, TX, USA
  11. Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
  12. Clinic of Endocrinology and Metabolic Diseases, Cantonal Hospital, Olten, Switzerland
  13. Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
  14. Internal Medicine Department & Obesity Clinic, Hasharon Hospital-Rabin Medical Center, Petach-Tikva, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Aims: The STEP 4 clinical trial programme investigated weight loss maintenance with continued subcutaneous semaglutide (a GLP-1 analogue) vs switching to placebo in overweight or obese participants reaching semaglutide 2.4 mg during a 20-week study run-in.

Methods: This was a randomised, quadruple-blind, placebo-controlled, phase 3 trial of 803 adults with a body mass index (BMI) ≥30 kg/m2 or ≥27 kg/m2 with ≥1 weight-related comorbidity, without diabetes, who reached 2.4 mg of once-weekly subcutaneous semaglutide following dose escalation over 20 weeks (NCT03548987). Participants were randomised 2:1 to continue semaglutide 2.4 mg or switch to placebo for 48 weeks, both with lifestyle intervention. The primary endpoint was body weight change between weeks 20─68. Treatment policy estimand results are presented.

Results: Mean (±SD) body weight was 107.2 (±22.7) kg at week 0 and 96.1 (±22.6) kg at randomisation (mean change −10.6%). In randomised participants (mean age 46 years, BMI 34.4 kg/m2; 84% white, 79% female), mean body weight change between weeks 20─68 was −7.9% (semaglutide 2.4 mg) vs +6.9% (placebo) (estimated treatment difference [ETD]: −14.8%; 95% CI: −16.0, −13.5; p<0.0001). Similar results were obtained with the trial product estimand. For participants continuing semaglutide 2.4 mg, body weight change from week 0─68 was −17.4%. Continued semaglutide 2.4 mg led to improvements in cardiometabolic risk factors vs placebo. During run-in, 5.3% of participants discontinued treatment due to adverse events (AEs); after randomisation, 2.4% (semaglutide 2.4 mg) and 2.2% (placebo) of patients discontinued because of AEs. Most frequent AEs with semaglutide 2.4 mg were nausea, diarrhoea and constipation (mostly transient and mild-to-moderate).

Conclusions: In adults with overweight or obesity, continued semaglutide 2.4 mg after dose escalation led to clinically relevant weight loss, while switching to placebo led to weight regain. These findings underscore the chronicity and relapsing nature of obesity and the need for continued treatment.