Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension.
Level 2 - randomized trial
Pre-specified off-treatment extension of an individual randomized controlled trial
PubMed 35441470 · doi:10.1111/dom.14725
What was done
In an exploratory off-treatment extension of the STEP 1 trial, 327 adults with overweight or obesity without diabetes who completed 68 weeks of once-weekly subcutaneous semaglutide 2.4 mg or placebo (both with lifestyle intervention) were followed for an additional 52 weeks (to week 120) after discontinuing all study treatments and lifestyle support.
What was found
From week 0 to week 68, mean weight loss was 17.3% (SD: 9.3%) with semaglutide and 2.0% (SD: 6.1%) with placebo. Following withdrawal, semaglutide and placebo participants regained 11.6 (SD: 7.7) and 1.9 (SD: 4.8) percentage points of body weight by week 120, leaving net weight reductions from baseline of 5.6% (SD: 8.9%) and 0.1% (SD: 5.8%), respectively. Most cardiometabolic improvements gained with semaglutide reverted toward baseline by week 120.
Why it matters
This study demonstrates that weight loss and cardiometabolic improvements achieved with semaglutide are largely lost upon treatment cessation, supporting the view that obesity requires ongoing management rather than short-term intervention.
Limits
The extension was exploratory and evaluated only a subset (327 of 1961) of the initial trial cohort. Because lifestyle interventions were withdrawn simultaneously with the drug, the effect of continued lifestyle support alone cannot be determined. Specific numeric outcomes for individual cardiometabolic risk factors were not reported in the abstract.