The short answer
In STEP 5, people assigned semaglutide maintained substantial average weight loss over two years. The average weight curve levelled off rather than continuing downward indefinitely. Maintaining a lower weight was part of the result.
Two years, two groups
Timothy Garvey and colleagues studied 304 adults with obesity, or overweight plus a weight-related condition, who did not have diabetes. Participants were randomly assigned weekly semaglutide 2.4 mg or placebo. Both groups received behavioral support around eating and physical activity. These were the study regimens, not instructions for choosing a dose.
The main comparison was at 104 weeks—two years. Researchers assessed the effect of assignment to treatment even if a participant stopped the study medicine or needed another intervention. That is different from reporting only the people who stayed on treatment throughout.
The main finding
Average weight change at two years was −15.2% with semaglutide, compared with −2.6% with placebo. The estimated difference was 12.6 percentage points in favor of semaglutide.
For an intuitive scale, 15.2% of a hypothetical 200-pound starting weight is about 30 pounds. That arithmetic illustrates the percentage; it is not a forecast for a particular person.
About 77% of the semaglutide group achieved at least 5% weight loss, compared with about 34% of the placebo group. Participants did not all have the same response.
Percentage of starting weight
Original chart based on the study. Values are reported group averages.
| Group or time | Average weight change |
|---|---|
| Semaglutide 2.4 mg | −15.2% |
| Placebo | −2.6% |
A plateau is a different question from losing progress
The average weight curve flattened around week 60 and the reduction was maintained through week 104. A flat line at a lower weight can represent maintenance—not necessarily a medicine that has stopped doing anything.
This is also why a chart showing only the speed of loss can miss something useful. “How much did people lose?” and “Did they keep it off while treatment continued?” are separate questions. STEP 5 gives evidence about both.
The trade-off: digestive side effects
Digestive adverse events were reported by 82.2% of participants receiving semaglutide and 53.9% receiving placebo. Most were mild or moderate. Those figures describe whether an event occurred, not constant symptoms for two years or the percentage of people who stopped treatment.
Who does this result represent?
This was a relatively small trial. Most participants were women, and 93.1% were White. It excluded people with diabetes. Those details matter when considering how closely its averages match other populations.
Both groups had behavioral support; the trial was not a comparison of medicine alone against doing nothing. It also did not answer what happens after stopping. For that question, STEP 1 extension follows a different group after treatment ended.
Sources
Garvey WT and colleagues. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nature Medicine, 2022. Full paper · DOI. Funded by Novo Nordisk.