Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension
- Design
- Randomized trial · 327 participants · Intermediate outcome
- Match to healthy normal-weight adults aged 55–75
- Different population[Auto] Participants had obesity/overweight without diabetes (age/BMI not reported in abstract); effects may be mediated by weight loss.
- Could weight loss explain it?
- Not applicable[Auto] Participants had obesity and/or type 2 diabetes and the abstract does not separate direct drug effects from weight loss or glycaemic improvement.
- Study tier
- Study tier 2[Auto] Randomized trial of moderate size; outcome type and follow-up limit certainty (auto-provisional).
- Assessment
- Version 2 · curated · Sep 13, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
One year after stopping semaglutide and lifestyle support, participants had regained two-thirds of the weight they lost and most metabolic improvements had faded.
01Findings
What the study reported
- Drugs
- Semaglutide
- Dose
- 2.4 mg weekly
- Route
- subcutaneous
- Treatment duration
- 68 weeks then 52 weeks off treatment
- Comparator
- placebo
- Primary outcome
- Exploratory: weight and cardiometabolic changes one year after withdrawal
- Effect
- Regained 11.6 percentage points of 17.3% loss (two-thirds); cardiometabolic variables reverted toward baseline
- 95% confidence interval
- Not extracted
- Follow-up
- 120 weeks
- Adverse events
- Not extracted
- Limitations
- Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.
Who was studied
- Obesity status
- BMI >= 30 or >= 27 with comorbidity
- Diabetes status
- excluded
- Sample size
- 1961
Study quality details
- Study design
- Randomized controlled trial
- Sample size
- 1961
- Randomization
- yes
- Blinding
- not stated
- Comparator
- placebo
- Follow up duration
- 68 weeks
- Outcome type
- unknown
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- not extracted
- Risk of bias
- exploratory off-treatment extension in a subset
- Funding conflicts
- unclear
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- Novo Nordisk
- Industry funded
- Yes
- Manufacturer
- Novo Nordisk
- Sponsor role
- Sponsor designed and analysed.
- Author conflicts
- Authors report Novo Nordisk and other industry relationships.
- Independent replication
- unknown
- Notes
- Authors declare relationships with the drug's manufacturer: Novo Nordisk
Funding is shown on every study and never used to score it.
03Claims
Claims this study bears on
- Stopping GLP-1 therapy leads to regain of most lost weight and reversal of cardiometabolic improvements.Supports
STEP 1 extension, n=327 exploratory.
04Source
The source, as retrieved
Abstract
[AIM] To explore changes in body weight and cardiometabolic risk factors after treatment withdrawal in the STEP 1 trial extension. [MATERIALS AND METHODS] STEP 1 (NCT03548935) randomized 1961 adults with a body mass index ≥ 30 kg/m2 (or ≥ 27 kg/m2 with ≥ 1 weight-related co-morbidity) without diabetes to 68 weeks of once-weekly subcutaneous semaglutide 2.4 mg (including 16 weeks of dose escalation) or placebo, as an 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 of treatment. This subset comprised all eligible participants from any site in Canada, Germany and the UK, and sites in the United States and Japan with the highest main phase recruitment. All analyses in the extension were exploratory. [RESULTS] Extension analyses included 327 participants. 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 treatment withdrawal, semaglutide and placebo participants regained 11.6 (SD: 7.7) and 1.9 (SD: 4.8) percentage points of lost weight, respectively, by week 120, resulting in net losses of 5.6% (SD: 8.9%) and 0.1% (SD: 5.8%), respectively, from week 0 to week 120. Cardiometabolic improvements seen from week 0 to week 68 with semaglutide reverted towards baseline at week 120 for most variables. [CONCLUSIONS] One year after withdrawal of once-weekly subcutaneous semaglutide 2.4 mg and lifestyle intervention, participants regained two-thirds of their prior weight loss, with similar changes in cardiometabolic variables. Findings confirm the chronicity of obesity and suggest ongoing treatment is required to maintain improvements in weight and health.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 13, 2026 | 35441470 first ingestion |