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 summarizes 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 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.
doi:10.1056/NEJMoa2032183 · PubMed: 33567185
Who Was in the Trial?
The trial enrolled 1,961 adults with a BMI of 30 or greater, or a BMI of 27 or greater with at least one weight-related comorbidity (such as high blood pressure, dyslipidaemia, or cardiovascular disease). Participants with type 2 diabetes were excluded from this arm. All participants received lifestyle intervention counselling alongside their assigned treatment.
What the Trial Measured
The primary endpoint was 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):
In the STEP 1 trial of semaglutide 2.4 mg (marketed as Wegovy®), mean weight reduction at week 68 was 14.9%, compared with 2.4% for placebo. These results apply to Wegovy® as studied and do not apply to compounded semaglutide. Individual results vary.
Participants achieving ≥5% weight reduction: 86.4% (Wegovy®) vs. 31.5% (placebo). Individual results vary.
Participants achieving ≥10% weight reduction: 69.1% (Wegovy®) vs. 12.0% (placebo). Individual results vary.
Participants achieving ≥15% weight reduction: 50.5% (Wegovy®) vs. 4.9% (placebo). Individual results vary.
All figures 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, escalating gradually from 0.25 mg over 16 weeks to a 2.4 mg maintenance dose. All participants in both groups received reduced-calorie diet and increased physical activity counselling throughout the 68-week trial.
What This Means for Our Program
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.
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.