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Randomized controlled trial

STEP 8: semaglutide (Wegovy) vs liraglutide (Saxenda)

At 68 weeks, weight changed by −15.8% with semaglutide and −6.4% with liraglutide (difference of −9.4 percentage points; 95% CI, −12.0 to −6.8); on placebo it changed by −1.9%.

Rubino DM et al. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial. JAMA, 2022. DOI: 10.1001/jama.2021.23619

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Key facts

Drugs
semaglutide and liraglutide
Design
Randomized controlled trial
Participants
338
Duration
68 weeks
Funding
Novo Nordisk
Registry
NCT04074161
Population
338 adults with a BMI of 30 or more (or 27 or more with at least one weight-related comorbidity), without diabetes, at 19 sites in the United States, randomized to semaglutide 2.4 mg once weekly (126), liraglutide 3.0 mg once daily (127) or placebo (85, two placebo groups analyzed together); mean age 49 years, 78.4% women, mean weight 104.5 kg and mean BMI 37.5.
Primary outcome
Percentage change in body weight at 68 weeks with semaglutide 2.4 mg once weekly versus liraglutide 3.0 mg once daily, both with diet and physical activity. The comparison between the two drugs was open-label; each was double-blinded against its own placebo.

What it found

Mean weight loss, % of starting weight · 68 weeks
  • Semaglutide 2.4 mg weekly−15.8%
  • Liraglutide 3.0 mg daily−6.4%
  • Placebo−1.9%

Difference (Semaglutide 2.4 mg weekly): −13.9 points vs placebo (subtraction).

Difference (Liraglutide 3.0 mg daily): −4.5 points vs placebo (subtraction).

Figures from the paperSee the results in a chart

At 68 weeks, weight changed by −15.8% with semaglutide and −6.4% with liraglutide (difference of −9.4 percentage points; 95% CI, −12.0 to −6.8); on placebo it changed by −1.9%. At least 10% of weight was lost by 70.9% on semaglutide and 25.6% on liraglutide, at least 15% by 55.6% and 12.0%, and at least 20% by 38.5% and 6.0%. The results include people who stopped treatment (treatment-policy estimand). Treatment was stopped for any reason by 13.5% on semaglutide and 27.6% on liraglutide; digestive adverse effects were similar (84.1% and 82.7%).

Limitations

Funded by Novo Nordisk, the maker of both drugs, which took part in the design, analysis and writing. The comparison between semaglutide and liraglutide was open-label: participants knew which of the two they were getting. Small sample, in a single country and without people with diabetes. People who could not tolerate 2.4 mg of semaglutide could continue on 1.7 mg, whereas people who could not tolerate 3.0 mg of liraglutide had to stop it and could restart the dose escalation, which may influence discontinuations.

What it means for you

In this head-to-head comparison, weekly semaglutide (Wegovy) reduced weight considerably more than daily liraglutide (Saxenda): 15.8% versus 6.4% on average over 68 weeks, and fewer people stopped treatment. It was a small, open-label trial funded by the maker of both drugs. Which treatment fits your case is something your doctor weighs.

Further reading

Related trials

  • semaglutide72 weeks

    STEP UP

    At 72 weeks, weight changed by −18.7% with semaglutide 7.2 mg, −15.6% with 2.4 mg and −3.9% with placebo.

  • semaglutide120 weeks

    STEP 1 (extension)

    From week 0 to week 68, weight fell by an average of 17.3% with semaglutide and 2.0% with placebo.

  • semaglutide104 weeks

    STEP 5

    At 104 weeks, weight changed by −15.2% with semaglutide 2.4 mg and −2.6% with placebo.

  • semaglutide68 weeks

    STEP 1

    Semaglutide 2.4 mg once weekly, together with a lifestyle intervention, reduced weight by an average of 14.9% at 68 weeks, compared with 2.4% on placebo.

Sources

The original paper and the records consulted for this summary, with the date they were accessed.

  1. JAMA.Rubino DM, et al. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial. JAMA. 2022;327(2):138-150.accessed .
  2. National Library of Medicine (PubMed).PubMed record PMID 35015037 (abstract).accessed .
  3. PubMed Central (National Library of Medicine).Full text PMC8753508 (estimands and funding).accessed .