Poster Presentation ANZOS Annual Scientific Meeting 2021

Efficacy and safety of once-weekly subcutaneous semaglutide 2.4mg in adults with overweight or obesity (STEP 1) (#213)

Samantha Hocking 1 2 , John PH Wilding 3 , Rachel L Batterham 4 , Salvatore Calanna 5 , Melanie Davies 6 7 , Luc F Van Gaal 8 , Ildiko Lingvay 9 , Barbara M McGowan 10 , Julio Rosenstock 11 , Marie TD Tran 5 , Thomas Wadden 12 , Sean Wharton 13 , Koutaro Yokote 14 15 , Niels Zeuthen 5 , Robert F Kushner 16
  1. Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney Central Clinical School, Sydney, NSW, Australia
  2. Department of Endocrinology, Royal Prince Alfred Hospital Sydney , Sydney, NSW, Australia
  3. Obesity and Endocrinology Research, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK
  4. University College London Centre for Obesity Research, Division of Medicine, University College London and National Institute of Health Research, UCLH Biomedical Research Centre and Centre for Weight Management and Metabolic Surgery, London, UK
  5. Novo Nordisk A/S, Søborg, Denmark
  6. Diabetes Research Centre, University of Leicester , Leicester, UK
  7. NIHR Leicester Biomedical Research Centre, Leicester General Hospital, Leicester, UK
  8. Department of Endocrinology, Diabetology and Metabolic Diseases, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium
  9. UT Southwestern Medical Center, Dallas, TX, USA
  10. Department of Diabetes and Endocrinology, Guy's and St Thomas' NHS Foundation Trust, London, UK
  11. Dallas Diabetes Research Center at Medical City, Dallas, TX, USA
  12. Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
  13. York University, McMaster University and Wharton Weight Management Clinic, Toronto, ON, Canada
  14. Department of Endocrinology, Hematology and Gerontology, Graduate School of Medicine, Chiba University, Chiba, Japan
  15. Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba , Japan
  16. Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

Aims: STEP 1 investigated the GLP-1 analogue, subcutaneous semaglutide, for weight management in adults with overweight or obesity.

Methods: This was a randomised, double-blind, placebo-controlled, phase 3 trial (NCT03548935) of adults with a body mass index (BMI) ≥30kg/m2 or ≥27kg/m2 with ≥1 weight-related comorbidity, without type 2 diabetes. Patients were randomised 2:1 to 68 weeks’ treatment with once-weekly subcutaneous semaglutide 2.4mg or placebo, adjunct to lifestyle intervention. Co-primary endpoints were percentage change in body weight and weight loss ≥5%. Two estimands were defined: treatment policy and trial product; results are presented for the treatment-policy estimand, unless stated otherwise. P-values for parameters marked with # were not controlled for multiplicity.

Results: 1961 randomised participants (mean age 46 years, body weight 105.3kg, BMI 37.9kg/m2; 74.1% female) were included. Mean body weight change from baseline to week 68 was −14.9% (semaglutide) vs −2.4% (placebo) (estimated treatment difference [ETD]: −12.4%; 95% CI: −13.4, −11.5; p<0.0001). Similar results were obtained with the trial product estimand:#–16.9% (semaglutide) vs –2.4% (placebo) (ETD: –14.4%; 95% CI: –15.3, –13.6; p<0.0001). Participants were more likely to achieve weight loss ≥5%, ≥10%, ≥15% and ≥20%# with semaglutide vs placebo (86.4% vs 31.5%, 69.1% vs 12.0%, 50.5% vs 4.9% and 32.0% vs 1.7%, respectively; p<0.0001 for all). Greater improvements were seen with semaglutide vs placebo in waist circumference, BMI#, systolic and diastolic# blood pressure, glycated haemoglobin#, fasting plasma glucose#, C‑reactive protein#, fasting lipid profile# and self-reported physical functioning (p<0.05 for all). No new safety signals with semaglutide were observed.

Conclusions: In overweight or obese adults, once-weekly subcutaneous semaglutide 2.4mg plus lifestyle intervention induced a mean weight loss of ~15% by week 68. Clinically beneficial weight loss ≥10% was achieved by over two-thirds of participants and ≥20% by one-third of participants, along with associated improvements in cardiometabolic risk factors and physical functioning.