Semaglutide: What the Clinical Trials Show

Semaglutide: What the Clinical Trials Show

Before our medical providers consider prescribing semaglutide, they review your health history against the published evidence base. This article summarises the key findings from the STEP 1 clinical trial — one of the primary Phase 3 studies supporting the FDA approval of semaglutide for chronic weight management. Individual results vary.

The STEP 1 Trial: Background

The STEP 1 trial (Semaglutide Treatment Effect in People with Obesity) was a randomised, double-blind, placebo-controlled trial. It was published in the New England Journal of Medicine in 2021:

Wilding JPH, Batterham RL, Calanna S, et al. "Once-Weekly Semaglutide in Adults with Overweight or Obesity." New England Journal of Medicine. 2021;384:989–1002.
https://www.nejm.org/doi/10.1056/NEJMoa2032183
Also available via PubMed: https://pubmed.ncbi.nlm.nih.gov/33567185/

Who Was in the Trial?

The trial enrolled 1,961 adults with a body mass index (BMI) of 30 or greater, or a BMI of 27 or greater with at least one weight-related comorbidity (such as high blood pressure, type 2 diabetes, or dyslipidaemia). Participants with type 2 diabetes were excluded from this specific trial arm. All participants received lifestyle intervention counselling alongside their assigned treatment.

What the Trial Measured

The primary endpoint was the percentage change in body weight from baseline to week 68. Key secondary endpoints included the proportion of participants achieving at least 5%, 10%, and 15% reductions in body weight.

What the Trial Found

As reported in Wilding et al. (2021), participants receiving once-weekly subcutaneous semaglutide 2.4 mg achieved a mean weight reduction of 14.9% from baseline at week 68, compared to 2.4% in the placebo group. Individual results vary.

Additional findings reported in the trial:

  • 86.4% of participants in the semaglutide group lost ≥5% of body weight, vs. 31.5% in the placebo group. Individual results vary.
  • 69.1% lost ≥10% of body weight in the semaglutide group, vs. 12.0% in the placebo group. Individual results vary.
  • 50.5% lost ≥15% of body weight in the semaglutide group, vs. 4.9% in the placebo group. Individual results vary.

All figures cited above are taken directly from Wilding et al., NEJM, 2021. Individual results vary.

How the Trial Was Conducted

Semaglutide was administered as a once-weekly subcutaneous injection. The dose was escalated gradually from 0.25 mg over a 16-week period to reach the full 2.4 mg maintenance dose. All participants in both the active and placebo groups received reduced-calorie diet and increased physical activity counselling throughout the trial.

What This Means for Our Programme

The STEP 1 results are part of the evidence base our physicians use when evaluating whether semaglutide may be appropriate for a given patient. A licensed clinician — not a quiz, not an algorithm — makes this determination based on your individual health history. Semaglutide is not right for everyone, and results vary significantly between individuals.

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All medical decisions are made solely by licensed healthcare professionals. Medications are prescribed only when medically necessary. GLP-1 medications are not suitable for everyone. Results may vary.

Results vary. Clinical trial results apply only to the FDA-approved branded medication specifically identified and do not apply to compounded medications. All medications must be prescribed by a licensed provider based on medical necessity.