Before tirzepatide, liraglutide 3.0 mg (Saxenda) was the only other GLP-1 approved for weight management. STEP 8 put the two Novo Nordisk drugs against each other.
What the trial asked
Whether once-weekly semaglutide 2.4 mg produces more weight loss than once-daily liraglutide 3.0 mg, both added to diet and physical activity counselling, in adults with overweight or obesity without diabetes.
Design
Randomised, open-label for the active comparison, 68 weeks, phase 3b, at 19 US sites from September 2019 to May 2021. Randomised 3:1:3:1 to semaglutide 2.4 mg (16-week escalation; n=126) or its matching placebo, or liraglutide 3.0 mg (4-week escalation; n=127) or its matching placebo. Each active drug was double-blinded against its own placebo; the semaglutide-versus-liraglutide comparison was open-label. The two placebo groups were pooled (n=85). Participants who could not tolerate 2.4 mg semaglutide could take 1.7 mg; those who could not tolerate 3.0 mg liraglutide stopped and could restart the 4-week titration.
Who was enrolled
338 adults with a BMI of 30 or greater, or 27 or greater with at least one weight-related comorbidity, without diabetes. Mean age 49 (SD 13); 265 (78.4 percent) women; mean weight 104.5 kg (SD 23.8); mean BMI 37.5 (SD 6.8). 319 (94.4 percent) completed the trial and 271 (80.2 percent) completed treatment.
Primary endpoint and result
Primary endpoint: percent change in body weight at week 68, semaglutide versus liraglutide.
| Arm | Mean weight change at week 68 |
|---|---|
| Semaglutide 2.4 mg weekly | -15.8% |
| Liraglutide 3.0 mg daily | -6.4% |
| Pooled placebo | -1.9% |
Difference, semaglutide versus liraglutide: -9.4 percentage points (95% CI -12.0 to -6.8; P less than 0.001). The comparisons with pooled placebo were supportive secondary endpoints.
Key secondary results
Confirmatory secondary endpoints, semaglutide versus liraglutide:
| Threshold | Semaglutide | Liraglutide | Odds ratio (95% CI) |
|---|---|---|---|
| 10% or more | 70.9% | 25.6% | 6.3 (3.5 to 11.2) |
| 15% or more | 55.6% | 12.0% | 7.9 (4.1 to 15.4) |
| 20% or more | 38.5% | 6.0% | 8.2 (3.5 to 19.1) |
All P less than 0.001.
Adverse events and discontinuation
Gastrointestinal adverse events: 84.1 percent with semaglutide and 82.7 percent with liraglutide. Discontinuation of treatment for any reason: 13.5 percent with semaglutide and 27.6 percent with liraglutide. The abstract does not break discontinuation down by cause.
Funding and registration
The abstract does not name the funder. ClinicalTrials.gov NCT04074161.
What this trial does not show
- The drug comparison was open-label, and the placebo groups were small (85 pooled).
- 338 participants at 19 US sites. The confidence interval on the primary difference runs from -12.0 to -6.8, a wide band.
- Liraglutide's short 4-week escalation and its restart rule for intolerance are not the same as semaglutide's 16-week escalation with a 1.7 mg fallback. Some of the discontinuation gap may reflect protocol design as much as the molecules.
- Nothing about tirzepatide. For semaglutide against tirzepatide, see SURMOUNT-5.
Where the numbers come from
PubMed abstract of the primary paper (PubMed 35015037), fetched 4 September 2026. The sibling site GLP-1s Explained has per-agent pages for both drugs.
Sources
Canonical URL: https://formblendsresearch.com/trials/step-8. Written by the FormBlends editorial team. This page is educational and is not medical advice; see the medical disclaimer.