STEP 8: weekly semaglutide versus daily liraglutide, head to head

Why this study matters

Semaglutide (Wegovy, Ozempic) and liraglutide (Saxenda, Victoza) belong to the same family of medicines, called GLP-1 receptor agonists. Before STEP 8, no large trial had compared the two weight-management doses against each other in the same people. Comparing numbers across separate trials is unreliable, because the people, support and time frames differ. STEP 8 is the one trial that puts them side by side, which is why Canadian readers weighing the two medicines often hear about it.

Who was in the study

STEP 8 enrolled 338 adults without diabetes at 19 sites in the United States. Enrolment ran from 11 September to 26 November 2019, and follow-up ended on 11 May 2021. Everyone had a BMI of 30 or more, or 27 or more with at least one weight-related health condition. BMI (body mass index) compares weight with height.

The mean age was 49 years. Most participants were women (265 people, 78.4%). Mean body weight at the start was 104.5 kg and mean BMI was 37.5. In total, 319 people (94.4%) completed the trial and 271 (80.2%) completed treatment.

What the researchers did

This was a randomized phase 3b trial lasting 68 weeks. People were assigned by chance in a 3:1:3:1 ratio to one of four groups: semaglutide 2.4 mg injected once a week (126 people), a matching weekly placebo, liraglutide 3.0 mg injected once a day (127 people), or a matching daily placebo. The two placebo groups were pooled, giving 85 people. Everyone received diet and physical activity counselling.

The comparison between semaglutide and liraglutide was open-label, meaning people knew which of the two active medicines they were taking. Each active medicine was blinded against its own placebo, so people on placebo did not know it.

Dose build-up differed. Semaglutide was increased over 16 weeks; liraglutide over 4 weeks. People who could not tolerate 2.4 mg of semaglutide could stay on 1.7 mg. People who could not tolerate 3.0 mg of liraglutide had to stop and could restart the 4-week build-up.

The main outcome was percentage change in body weight at week 68, semaglutide versus liraglutide. Confirmatory secondary outcomes were the share of people losing at least 10%, 15% and 20% of their starting weight. Comparisons with pooled placebo were supportive only.

What they found

Mean weight change from the start to week 68 was -15.8% with semaglutide and -6.4% with liraglutide (R32-C11). The difference was -9.4 percentage points, with a 95% confidence interval of -12.0 to -6.8. A confidence interval is the range where the true difference most likely sits. Weight change with pooled placebo was -1.9%.

The odds ratios for reaching these marks with semaglutide versus liraglutide were 6.3 (95% CI 3.5 to 11.2) for 10%, 7.9 (4.1 to 15.4) for 15%, and 8.2 (3.5 to 19.1) for 20%. An odds ratio above 1 means the outcome was more likely with semaglutide.

Side effects and people who stopped

Treatment stopped for any reason in 13.5% of people assigned semaglutide and 27.6% assigned liraglutide (R32-C12). Stomach and gut side effects were reported by 84.1% of people on semaglutide and 82.7% on liraglutide. The summary we reviewed does not report how many people stopped specifically because of side effects, or the stopping rate in the placebo group.

What this study does not tell you

• The active comparison was open-label. Knowing which medicine you are on can affect behaviour and reporting.
• The two medicines had different build-up and tolerability rules. People who struggled with liraglutide had to stop and restart, which may have contributed to the higher stopping rate.
• The placebo comparisons were supportive only, not the main test.
• The trial ran only at US sites, and 78.4% of participants were women.
• No one had diabetes, and the trial did not measure heart or other health events.
• It does not tell you what happens after either medicine is stopped.
• Our data extraction relied on the abstract only, because the full text could not be retrieved.

What it means in Canada

STEP 8 is a direct comparison of two medicines that are both used for weight management, so it is more informative than lining up separate trials. It does not tell you which medicine suits you, what it costs, or whether it is covered. See semaglutide in Canada, public drug coverage by province and compare services.

Related reading

Other studies in this library that bear on the same question.

Source