Safety profile of semaglutide versus placebo in the SELECT study: a randomized controlled trial

Authors

• Robert F. Kushner, Northwestern University Feinberg School of Medicine, Chicago, IL
• Donna H. Ryan, Pennington Biomedical Research Center, Baton Rouge, LA
• John Deanfield, University College London, London, UK
• Alexander Kokkinos, National and Kapodistrian University of Athens, Athens, Greece
• Cintia Cercato, University of São Paulo, São Paulo, Brazil
• John Wilding, University of Liverpool, Liverpool, UK
• Bartolome Burguera, Cleveland Clinic, Cleveland, OH
• Chau-Chung Wu, National Taiwan University Hospital, Taipei, Taiwan
• Anca-Elena Craciun, Iuliu Hațieganu University of Medicine and Pharmacy Cluj-Napoca, Cluj, Romania
• Denes Pall, University of Debrecen, Debrecen, Hungary
• Irene Hramiak, Western University, London, Ontario, Canada
• Jøran Hjelmesæth, Vestfold Hospital Trust, Tønsberg, Norway
• Nina M. Harder-Lauridsen, Novo Nordisk A/S, Søborg, Denmark
• Petra Weimers, Novo Nordisk A/S, Søborg, Denmark
• Ole Kleist Jeppesen, Novo Nordisk A/S, Søborg, Denmark
• Klaus Kallenbach, Novo Nordisk A/S, Søborg, Denmark
• A Michael Lincoff, Case Western Reserve University, Cleveland, OH
• Ildiko Lingvay, UT Southwestern Medical Center, Dallas, TX

Document Type

Article

Publication Date

2-13-2025

Publication Title

Obesity

Abstract

Objective: The objective of this study was to assess safety of once-weekly subcutaneous semaglutide 2.4 mg versus placebo, beyond reduction in major adverse cardiovascular events, in patients with established cardiovascular disease and overweight or obesity. Methods: Safety data focused on serious adverse events (SAEs), all adverse events (AEs) leading to permanent treatment discontinuation irrespective of seriousness, and prespecified AEs of special interest irrespective of seriousness. Tests of treatment differences were determined by two-sided p values. Results: The proportion of patients with SAEs was lower with semaglutide versus placebo (33.4% vs. 36.4%; p < 0.001), primarily driven by cardiac disorders (11.5% vs. 13.5%; p < 0.001). The proportion of patients with AEs leading to discontinuation was higher with semaglutide versus placebo (16.6% vs. 8.2%; p < 0.001), a difference driven by gastrointestinal disorders (10.0% vs. 2.0%); however, proportions due to SAEs leading to discontinuation were similar (3.6% vs. 4.1%). Suicide/self-injury SAEs were low and balanced between groups (0.11% in both groups). Gallbladder-related disorders were more frequent with semaglutide versus placebo (2.8% vs. 2.3%; p = 0.04), mainly driven by cholelithiasis (1.4% vs. 1.1%), whereas proportions of cholecystitis were similar between groups (0.6% vs. 0.6%). Conclusions: The long-term safety profile observed in the Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity (SELECT) study is consistent with previously reported semaglutide studies. No new safety concerns were identified for once-weekly semaglutide 2.4 mg.

First Page

452

Last Page

462

DOI

10.1002/oby.24222

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

Recommended Citation

Kushner, Robert F.; Ryan, Donna H.; Deanfield, John; Kokkinos, Alexander; Cercato, Cintia; Wilding, John; Burguera, Bartolome; Wu, Chau-Chung; Craciun, Anca-Elena; Pall, Denes; Hramiak, Irene; Hjelmesæth, Jøran; Harder-Lauridsen, Nina M.; Weimers, Petra; Jeppesen, Ole Kleist; Kallenbach, Klaus; Lincoff, A Michael; and Lingvay, Ildiko, "Safety profile of semaglutide versus placebo in the SELECT study: a randomized controlled trial" (2025). LSU-LCMC Cancer Center Faculty Publications. 164.
https://digitalscholar.lsuhsc.edu/llcc_facpubs/164
10.1002/oby.24222