STEP 1 trial results showed average weight loss of 14.9% with semaglutide and 2.4% with placebo, an inactive injection, over 68 weeks. Both groups received help with food and physical activity. That's the source of the often-quoted “about 15%” figure. It describes a group average, with people above and below it.
What question did the STEP 1 semaglutide study ask?
Could a weekly semaglutide injection, added to lifestyle support, produce greater weight loss than lifestyle support with placebo? John Wilding and colleagues reported the answer in the New England Journal of Medicine in 2021.
The study enrolled 1,961 adults aged 18 or older; their average age was 46. Everyone had a BMI, a measure of weight relative to height, of at least 30, or at least 27 with a weight-related condition such as high blood pressure. Nobody had diabetes. Participants reported at least one unsuccessful attempt to lose weight through diet.
Other exclusions included previous weight-loss surgery, recent weight-loss medication use, and chronic or recent pancreatitis, inflammation of the pancreas. These boundaries matter when applying the findings to someone outside that group.
Participants were assigned by chance: 1,306 to semaglutide and 655 to placebo. Neither participants nor investigators knew the assignment. The trial registration, NCT03548935, records the planned study.
The intended semaglutide dose was 2.4 mg weekly, reached through gradual increases over 16 weeks. Both groups had counseling every four weeks, with a reduced-calorie eating plan and a physical-activity goal. The semaglutide timeline explains the changing curve; the prescriber sets an individual's actual dose.
How the researchers measured success
The primary endpoints, the two main measurements chosen beforehand, were percentage weight change and the share losing at least 5% by week 68.
The main analysis included people who stopped treatment or received other weight-management help, with estimates used for missing measurements. A separate analysis asking what would happen if everyone stayed on the assigned treatment found a larger semaglutide average: 16.9%. Those figures answer different questions. The headline result is 14.9%.
STEP 1 trial results at 68 weeks
Average weight change was −14.9% with semaglutide versus −2.4% with placebo. The paper's estimated difference was −12.4 percentage points, the gap between the two percentages, calculated before rounding those averages.
About half of semaglutide participants with a week-68 measurement lost at least 15%. About one in three lost at least 20%.
| Loss from starting weight | Semaglutide | Placebo |
|---|---|---|
| At least 5% | 86.4% | 31.5% |
| At least 10% | 69.1% | 12.0% |
| At least 15% | 50.5% | 4.9% |
| At least 20% | 32.0% | 1.7% |
These percentages use the participants with measurements available at week 68: 1,212 and 577, respectively. The 20% threshold was an additional outcome, outside the main sequence of statistical tests. The published paper, Table 2 and Figure 1, gives the full results.
Secondary measurements went beyond weight. Waist circumference changed by −13.54 versus −4.13 cm; systolic blood pressure, the top number, changed by −6.16 versus −1.06 mm Hg, the units used for blood pressure. Triglycerides, a type of blood fat, also fell.
Physical-function questionnaires asked how people managed everyday activities. Scores rose 2.21 versus 0.41 points on the general SF-36 questionnaire and 14.67 versus 5.25 on the weight-focused IWQOL-Lite-CT questionnaire. These were reported experiences, not strength tests. The guide to what 15% weight loss means puts those secondary measurements in everyday terms.
What side effects appeared in the paper?
About three in four semaglutide participants reported stomach or bowel problems. Most were temporary and mild to moderate, but some people stopped treatment because of them.
An adverse event is a health problem recorded during a study; recording it does not establish that the medicine caused it. These are selected rows from the paper's Table 3, using all 1,306 semaglutide and 655 placebo participants.
| Recorded event or treatment stop | Semaglutide | Placebo |
|---|---|---|
| Any stomach or bowel disorder | 74.2% | 47.9% |
| Serious events, such as those requiring hospitalization | 9.8% | 6.4% |
| Nausea | 44.2% | 17.4% |
| Diarrhea | 31.5% | 15.9% |
| Vomiting | 24.8% | 6.6% |
| Constipation | 23.4% | 9.5% |
| Stopped because of any adverse event | 7.0% | 3.1% |
| Stopped because of stomach or bowel events | 4.5% | 0.8% |
| Gallbladder-related disorders | 2.6% | 1.2% |
Gallbladder problems were mostly gallstones. The 4.5% figure concerns digestive problems specifically; it is not the overall treatment-stop rate. Headache was also recorded, in 15.2% of the semaglutide group versus 12.2% on placebo; does semaglutide cause headaches looks at that row.
What critics wanted to know next
In an accompanying NEJM editorial, Julie Ingelfinger and Clifford Rosen questioned how well the study represented the wider population and whether results would last. Roughly three-quarters of participants were women and three-quarters were White. Novo Nordisk funded the trial and helped design and analyze it.
The editorial also called for comparisons with other treatments. Tirzepatide became one such alternative: SURMOUNT-5, published in NEJM in 2025, compared it directly with semaglutide. STEP 1 itself cannot rank the two. The broader semaglutide results guide covers that comparison.
What later studies added
The STEP 1 extension, Wilding and colleagues, Diabetes, Obesity and Metabolism, 2022, followed 327 participants after medication and lifestyle support ended. In that subgroup, the semaglutide arm had lost 17.3% before stopping and regained 11.6 percentage points over the following year, leaving a 5.6% net loss. That's about two-thirds regained. It was a smaller follow-up group, and both forms of support stopped together.
STEP 5, Garvey and colleagues, Nature Medicine, 2022, followed 304 adults for two years. Average weight change was −15.2% with continued semaglutide versus −2.6% with placebo at week 104.
SELECT, published in NEJM in 2023, tested heart and stroke outcomes in adults with existing cardiovascular disease, meaning disease of the heart or blood vessels. Those outcomes needed their own trial; better blood-pressure readings in STEP 1 could not establish them. The SELECT trial explainer covers that separate question.
As of September 10, 2026, the day this article was written, a combined analysis published August 29, 2026 in the International Journal of Obesity brought together nine trials involving 6,239 adults without diabetes. It found 12.04 percentage points more weight loss with semaglutide than placebo. Differences in doses, populations and study length limit how directly that pooled figure applies to one person; it does not replace STEP 1's own result.
What this means for a prescription
STEP 1 gives a provider evidence about one formulation, dose and population. It did not test Promise's preparation.
Through Promise, semaglutide is dispensed as a compounded medication, prepared by a licensed pharmacy for an individual prescription, which is different from an FDA-approved product: the formulation offered here is not FDA-approved. As checked September 10, 2026, the FDA's compounding explanation states that these preparations do not undergo its review for safety, effectiveness or quality before marketing.
A licensed provider may still prescribe a compounded formulation; that decision is between the patient and the doctor. At Promise, a licensed provider reviews every request, and not everyone qualifies. Trial averages help inform that conversation alongside medical history, current medicines and manageable side effects.