Once-Weekly Semaglutide in Adults with Overweight or Obesity
- Design
- Randomized trial · 1961 participants · Intermediate outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationObesity without diabetes; landmark weight-loss trial; DXA substudy (full text) showed lean mass fell alongside fat mass.
- 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 1[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.
Landmark trial: semaglutide 2.4 mg produced 15% weight loss over 68 weeks in adults with obesity. Included for context and for its body-composition substudy showing proportional lean-mass loss.
01Findings
What the study reported
- Drugs
- Semaglutide
- Dose
- 2.4 mg weekly
- Route
- subcutaneous
- Treatment duration
- 68 weeks
- Comparator
- placebo
- Primary outcome
- Percent change in body weight; >=5% weight loss at week 68
- Effect
- -14.9% vs -2.4% (difference -12.4 pp)
- 95% confidence interval
- -13.4 to -11.5
- P value
- <0.001
- Follow-up
- 68 weeks
- Adverse events
- GI events most common; discontinuation for GI events 4.5% vs 0.8%.
- Limitations
- Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.
Who was studied
- Bmi min
- 30
- 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
- double-blind
- 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
- CI reported: 95% confidence interval [CI], -13
- Risk of bias
- not assessed (auto)
- Funding conflicts
- yes
- 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 relationships; sponsor co-authors.
- 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.
04Source
The source, as retrieved
Abstract
[BACKGROUND] Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed. [METHODS] In this double-blind trial, we enrolled 1961 adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or greater (≥27 in persons with ≥1 weight-related coexisting condition), who did not have diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary end points were the percentage change in body weight and weight reduction of at least 5%. The primary estimand (a precise description of the treatment effect reflecting the objective of the clinical trial) assessed effects regardless of treatment discontinuation or rescue interventions. [RESULTS] The mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group as compared with -2.4% with placebo, for an estimated treatment difference of -12.4 percentage points (95% confidence interval [CI], -13.4 to -11.5; P<0.001). More participants in the semaglutide group than in the placebo group achieved weight reductions of 5% or more (1047 participants [86.4%] vs. 182 [31.5%]), 10% or more (838 [69.1%] vs. 69 [12.0%]), and 15% or more (612 [50.5%] vs. 28 [4.9%]) at week 68 (P<0.001 for all three comparisons of odds). The change in body weight from baseline to week 68 was -15.3 kg in the semaglutide group as compared with -2.6 kg in the placebo group (estimated treatment difference, -12.7 kg; 95% CI, -13.7 to -11.7). Participants who received semaglutide had a greater improvement with respect to cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received placebo. Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%]). [CONCLUSIONS] In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight. (Funded by Novo Nordisk; STEP 1 ClinicalTrials.gov number, NCT03548935).
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 13, 2026 | 33567185 first ingestion |