Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity
Authors: Domenica Rubino, Niclas Abrahamsson, Melanie Davies, Dan Hesse, Frank L. Greenway, Camilla Jensen, Ildiko Lingvay, Ofri Mosenzon, Julio Rosenstock, Miguel A. Rubio, Gottfried Rudofsky, Sayeh Tadayon, Thomas A. Wadden, Dror Dicker, Mette Friberg, Anders Sjödin, Dror Dicker, Gabriella Segal, Ofri Mosenzon, Muhammad Sabbah, Yael Sofer, Victor Vishlitzky, Eelco W. Meesters, Mirelle Serlie, Arianne van Bon, Helena Cardoso, Paula Freitas, Pedro Carneiro de Melo, Margarida Monteiro, Mariana Monteiro, Dírcea Rodrigues, Aysha Badat, Pankaj Joshi, Gulam Latiff, Essack A. Mitha, Hans H. Snyman, Elane van Nieuwenhuizen, Olga González Albarrán, Assumpta Caixas, Carmen de al Cuesta, Pedro Pablo Garcia Luna, Cristobal Morales Portillo, Pedro Mezquita Raya, Miguel Angel Rubio, Niclas Abrahamsson, Johan Hoffstedt, Fredrik von Wowern, Erik Uddman, Birgit Bach-Kliegel, Felix Beuschlein, Stefan Bilz, Alain Golay, Gottfried Rudofsky, Christopher Strey, Galyna Fadieienko, Nataliia Kosei, Tetiana Tatarchuk, Valentyna Velychko, Olesya Zinych, Stephen L. Aronoff, Harold E. Bays, Andrew P. Brockmyre, Robert S. Call, Charles Crump, Cyrus V. Desouza, Valerie Espinosa, Almena L. Free, Winston H. Gandy, Steven A. Geller, Gregory M. Gottschlich, Frank L. Greenway, Laurie Han-Conrad, Wayne Harper, Lee Herman, Mitzie Hewitt, Priscilla Hollander, Steven R. Kaster, Anastasios Manessis, Frederick A. Martin, Robert E. McNeill, Alexander V. Murray, Paul C. Norwood, John C.H. Reed, Julio Rosenstock, Domenica M. Rubino, Martin J. Schear, Mark L. Warren
Journal: JAMA (2021)

The effect of continuing vs withdrawing treatment with semaglutide, a glucagon-like peptide 1 receptor agonist, on weight loss maintenance in people with overweight or obesity is unknown.To compare continued once-weekly treatment with subcutaneous semaglutide, 2.4 mg, with switch to placebo for weight maintenance (both with lifestyle intervention) in adults with overweight or obesity after a 20-week run-in with subcutaneous semaglutide titrated to 2.4 mg weekly.Randomized, double-blind, 68-week phase 3a withdrawal study conducted at 73 sites in 10 countries from June 2018 to March 2020 in adults with body mass index of at least 30 (or ≥27 with ≥1 weight-related comorbidity) and without diabetes.A total of 902 participants received once-weekly subcutaneous semaglutide during run-in. After 20 weeks (16 weeks of dose escalation; 4 weeks of maintenance dose), 803 participants (89.0%) who reached the 2.4-mg/wk semaglutide maintenance dose were randomized (2:1) to 48 weeks of continued subcutaneous semaglutide (n = 535) or switched to placebo (n = 268), plus lifestyle intervention in both groups.The primary end point was percent change in body weight from week 20 to week 68; confirmatory secondary end points were changes in waist circumference, systolic blood pressure, and physical functioning (assessed using the Short Form 36 Version 2 Health Survey, Acute Version [SF-36]).Among 803 study participants who completed the 20-week run-in period (with a mean weight loss of 10.6%) and were randomized (mean age, 46 [SD, 12] years; 634 [79%] women; mean body weight, 107.2 kg [SD, 22.7 kg]), 787 participants (98.0%) completed the trial and 741 (92.3%) completed treatment. With continued semaglutide, mean body weight change from week 20 to week 68 was -7.9% vs +6.9% with the switch to placebo (difference, -14.8 [95% CI, -16.0 to -13.5] percentage points; P < .001). Waist circumference (-9.7 cm [95% CI, -10.9 to -8.5 cm]), systolic blood pressure (-3.9 mm Hg [95% CI, -5.8 to -2.0 mm Hg]), and SF-36 physical functioning score (2.5 [95% CI, 1.6-3.3]) also improved with continued subcutaneous semaglutide vs placebo (all P < .001). Gastrointestinal events were reported in 49.1% of participants who continued subcutaneous semaglutide vs 26.1% with placebo; similar proportions discontinued treatment because of adverse events with continued semaglutide (2.4%) and placebo (2.2%).Among adults with overweight or obesity who completed a 20-week run-in period with subcutaneous semaglutide, 2.4 mg once weekly, maintaining treatment with semaglutide compared with switching to placebo resulted in continued weight loss over the following 48 weeks.ClinicalTrials.gov Identifier: NCT03548987.