Controlled study
STEP 1: weight change at 68 weeks
In STEP 1, mean weight change was −14.9% with semaglutide and −2.4% with placebo at 68 weeks; the published adjusted difference was −12.4 percentage points (95% CI −13.4 to −11.5).
The STEP 1 abstract reports discontinuation due to gastrointestinal events in 59 participants (4.5%) receiving semaglutide and five (0.8%) receiving placebo.
Weight results during 68 or 72 treatment weeks and a two-week sleep intervention answer different questions from a withdrawal comparison after initial treatment. SURMOUNT-4 provides that specific comparison for 52 weeks after randomization.
- Evidence design
- Randomized comparison
- Population
- Adults without diabetes with BMI >=30 kg/m2, or >=27 kg/m2 with at least one weight-related coexisting condition; lifestyle intervention in both groups.
- Assessment period
- Baseline to week 68; During the trial; precise safety window not verified
- Reported units
- percentage points; % change; %
Keep in view
- The result concerns 68 weeks of treatment; it does not establish maintenance after withdrawal.
- The published adjusted difference is −12.4 pp and must not be replaced by subtraction of rounded arm means.
See study details — STEP 1
Study design and methods
Randomized comparison
Randomized, double-blind, placebo-controlled trial; allocation 2:1; 68 weeks; phase 3.
Population
Adults without diabetes with BMI >=30 kg/m2, or >=27 kg/m2 with at least one weight-related coexisting condition; lifestyle intervention in both groups.
- Outcome definition
- Percent change in body weight from baseline
- Assessment period
- Value
- 68
- Unit
- weeks
- Reported statistic
- Mean
- Unit
- % change from baseline
- Randomized participants
- 1961
- Estimand and analysis rules
- Name
- treatment-policy primary estimand
- Definition
- Treatment effect assessed regardless of treatment discontinuation or rescue interventions, as described in the primary publication abstract.
- Analysis population
- FAS consists of all randomized participants (1306 semaglutide; 655 placebo).
Extracted outcomes
| Outcome and group | Reported value | Assessment period | Sample and denominators | Uncertainty |
|---|---|---|---|---|
| Percent change in body weight Semaglutide Effect estimate | -14.9 % change Mean Unit: % change | Baseline to week 68 Study weeks 0–68 | Reported N: 1306 — full analysis population
| Arm confidence interval not verified; no reconstruction was performed. |
| Percent change in body weight Placebo Effect estimate | -2.4 % change Mean Unit: % change | Baseline to week 68 Study weeks 0–68 | Reported N: 655 — full analysis population
| Arm confidence interval not verified; no reconstruction was performed. |
| Percent change in body weight Semaglutide minus placebo Effect estimate | -12.4 percentage points adjusted mean difference Unit: percentage points | Baseline to week 68 Study weeks 0–68 | Reported N: 1961 — combined full analysis population
| 95% confidence interval: -13.4 to -11.5 Reported p-value: <0.001 (Between-group comparison) |
| Discontinuation due to gastrointestinal events Semaglutide 2.4 mg weekly Descriptive result; not an effect estimate | 4.5 % reported event percentage Exact numerator: 59 Unit: % | During the trial; precise safety window not verified | Reported N: Not reported or not verified — outcome-specific denominator not verified
| Confidence interval for this event was not verified; descriptive count or percentage. |
| Discontinuation due to gastrointestinal events Placebo Descriptive result; not an effect estimate | 0.8 % reported event percentage Exact numerator: 5 Unit: % | During the trial; precise safety window not verified | Reported N: Not reported or not verified — outcome-specific denominator not verified
| Confidence interval for this event was not verified; descriptive count or percentage. |
Percent change in body weight — Semaglutide: extraction context
- Outcome role
- Not specified in the consulted scope
- Scale reference
- baseline_body_weight
- Estimand and analysis rules
- Name
- treatment-policy primary estimand
- Definition
- Treatment effect assessed regardless of treatment discontinuation or rescue interventions, as described in the primary publication abstract.
- Extraction location
- Original article abstract; arm sample sizes cross-checked against registry participant flow
Percent change in body weight — Placebo: extraction context
- Outcome role
- Not specified in the consulted scope
- Scale reference
- baseline_body_weight
- Estimand and analysis rules
- Name
- treatment-policy primary estimand
- Definition
- Treatment effect assessed regardless of treatment discontinuation or rescue interventions, as described in the primary publication abstract.
- Extraction location
- Original article abstract; arm sample sizes cross-checked against registry participant flow
Percent change in body weight — Semaglutide minus placebo: extraction context
- Outcome role
- Not specified in the consulted scope
- Scale reference
- Difference in percent change
- Estimand and analysis rules
- Name
- treatment-policy primary estimand
- Definition
- Treatment effect assessed regardless of treatment discontinuation or rescue interventions, as described in the primary publication abstract.
- Extraction location
- Published comparison; SURMOUNT-5 contrast CI verified in official registry
- Reported difference; not recomputed from rounded arm means.
Discontinuation due to gastrointestinal events — Semaglutide 2.4 mg weekly: extraction context
- Outcome role
- Descriptive safety outcome
- Extraction location
- Original article abstract, safety results
- The safety denominator was not inferred from the randomized arm size.
Discontinuation due to gastrointestinal events — Placebo: extraction context
- Outcome role
- Descriptive safety outcome
- Extraction location
- Original article abstract, safety results
- The safety denominator was not inferred from the randomized arm size.
What the curated evidence supports
- In STEP 1, mean weight change was −14.9% with semaglutide and −2.4% with placebo at 68 weeks; the published adjusted difference was −12.4 percentage points (95% CI −13.4 to −11.5).
- The STEP 1 abstract reports discontinuation due to gastrointestinal events in 59 participants (4.5%) receiving semaglutide and five (0.8%) receiving placebo.
- Weight results during 68 or 72 treatment weeks and a two-week sleep intervention answer different questions from a withdrawal comparison after initial treatment. SURMOUNT-4 provides that specific comparison for 52 weeks after randomization.
Limitations
- The result concerns 68 weeks of treatment; it does not establish maintenance after withdrawal.
- The published adjusted difference is −12.4 pp and must not be replaced by subtraction of rounded arm means.
Verification scope
Verified through 2026-11-04 within the consulted scope.
- Bibliographic metadata checked
- Yes
- Original article abstract consulted
- Yes
- Full-text consultation
- Not consulted
- Official trial registry consulted
- Yes
- Statistical analysis plan consulted
- No
- Verification boundary
- Verification is limited to the specific fields and sources consulted; it is not a full systematic appraisal or GRADE rating.
Source record
Once-Weekly Semaglutide in Adults with Overweight or Obesity (2021). The New England journal of medicine.
Source identifiers
- Article DOI: 10.1056/NEJMoa2032183
- PubMed record 33567185
- Trial registration: NCT03548935
- Structured registry: NCT03548935