Clinical trials
STEP 1: semaglutide weight-loss results
The landmark trial that established semaglutide 2.4 mg as a highly effective weight-loss therapy.
Quick Answer
STEP 1 (NEJM, 2021) randomized about 1,961 adults with obesity (without diabetes) to once-weekly semaglutide 2.4 mg or placebo for 68 weeks, with lifestyle support. Mean weight reduction was about 14.9% with semaglutide versus 2.4% with placebo; roughly 86% lost at least 5%, about half lost 15% or more, and about a third lost 20% or more. Compounded semaglutide is not FDA-approved.
Key Facts
- ~1,961 adults with obesity, without diabetes; 68 weeks
- Mean weight change: about −14.9% (semaglutide) vs −2.4% (placebo)
- ~86% achieved ≥5%; ~50% ≥15%; ~32% ≥20%
- Also improved waist, blood pressure and metabolic markers
- Studied the branded product; compounded semaglutide is not FDA-approved
The question and design
STEP 1 asked how much weight adults with obesity (but not diabetes) could lose on semaglutide. Participants received once-weekly semaglutide 2.4 mg or placebo for 68 weeks, both with lifestyle counseling. Co-primary endpoints were percent change in body weight and the proportion losing at least 5%.
The results
Mean weight reduction was approximately 14.9% with semaglutide versus 2.4% with placebo. The proportions reaching higher thresholds were striking for a medication: about 86% lost at least 5%, roughly half lost 15% or more, and about a third lost 20% or more — results that had previously been associated mainly with surgery.
STEP 1: mean weight change at 68 weeks
Beyond the scale
Treated participants also saw improvements in waist circumference, blood pressure and several metabolic markers, consistent with the broad cardiometabolic benefits of meaningful weight loss. Gastrointestinal side effects were the most common adverse events and were mostly mild to moderate.
How to read it
STEP 1 was large, randomized and placebo-controlled — strong evidence — but trial averages hide wide individual variation, and participants were closely supported. It studied the branded product over 68 weeks; durability after stopping is addressed in STEP 4 and the regain literature. Compounded semaglutide is not FDA-approved.
Frequently asked questions
How much weight did people lose in STEP 1?
Mean weight reduction was about 14.9% over 68 weeks with semaglutide 2.4 mg, versus about 2.4% with placebo.
Does everyone lose that much?
No — 14.9% is the average; individual results vary widely, with some people losing much more and others less.
References
- Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1). N Engl J Med. 2021;384:989-1002.
- Garvey WT, et al. Two-year effects of semaglutide in adults with overweight or obesity (STEP 5). Nat Med. 2022;28:2083-2091.
- U.S. Food and Drug Administration. Wegovy, Ozempic and Rybelsus (semaglutide) prescribing information. Novo Nordisk.
Citations are for educational reference; this article summarizes published research in plain language and is not medical advice.
Bottom Line
STEP 1 showed semaglutide 2.4 mg produced about 15% average weight loss over 68 weeks — a landmark result. Averages are not guarantees, and suitability is an individual clinical decision.
Related from the Journal
STEP 2
Semaglutide in obesity with type 2 diabetes.
STEP 4
What happens when you stop.
Semaglutide vs semaglutide
How the numbers compare.