“Weight Regain and Cardiometabolic Effects After Withdrawal of Semaglutide: the STEP 1 Trial Extension”, John P. H. Wilding, Rachel L. Batterham, Melanie Davies, Luc F. Van Gaal, Kristian Kandler, Katerina Konakli, Ildiko Lingvay, Barbara M. McGowan, Tugce Kalayci Oral, Julio Rosenstock, Thomas A. Wadden, Sean Wharton, Koutaro Yokote, Robert F. Kushner2022-04-19 ()⁠:

Aim: To explore changes in body weight and cardiometabolic risk factors after treatment withdrawal in the STEP 1 trial extension.

Method & Materials: STEP 1 (NCT03548935) randomized 1,961 adults with body mass index ≥30 kg⁄m2 (or ≥ 27 kg⁄m2 with ≥1 weight-related comorbidity) without diabetes to 68-weeks’ once-weekly subcutaneous semaglutide 2.4 mg (including 16-weeks’ dose-escalation) or placebo, as adjunct to lifestyle intervention. At week 68, treatments (including lifestyle intervention) were discontinued. An off-treatment extension assessed for a further year a representative subset of participants who had completed 68 weeks’ treatment. This subset comprised all eligible participants from any site in Canada, Germany and the UK, and sites in the US and Japan with the highest main phase recruitment. All analyses in the extension were exploratory.

Results: Extension analyses included 327 participants. From week 0–68, mean weight loss was 17.3% (SD: 9.3) with semaglutide and 2.0% (6.1) with placebo. Following treatment withdrawal, semaglutide and placebo participants regained 11.6 (7.7) and 1.9 (4.8) percentage points of lost weight, respectively, by week 120, resulting in net losses of 5.6% (8.9) and 0.1% (5.8), respectively, from week 0–120. Cardiometabolic improvements seen from week 0–68 with semaglutide reverted towards baseline at week 120 for most parameters.

Figure 1: Change from baseline in body weight by week for: …participants in the semaglutide arm, grouped by categorical weight loss from weeks 0–68

Conclusion: 1 year after withdrawal of once-weekly subcutaneous semaglutide 2.4 mg and lifestyle intervention, participants regained 2⁄3rds of their prior weight loss, with similar changes in cardiometabolic parameters. Findings confirm the chronicity of obesity and suggest ongoing treatment is required to maintain improvements in weight and health.

[Keywords: antiobesity drug, clinical trial, GLP-1 analogue, obesity therapy, phase III study, weight control]