Randomised controlled trials
In the trials below, people were assigned at random to take Semaglutide or a dummy pill (placebo). All the weight loss figures are averages: how much body weight fell from the start.
| Trial | Key result | Source |
|---|---|---|
| [1]STEP 1 | 14.9% mean weight loss. 86% achieved ≥5% loss; 69% achieved ≥10%; 50% achieved ≥15%. Nausea 44% vs. 16% placebo; diarrhoea 30% vs. 16%; vomiting 24% vs. 6%; constipation 24% vs. 11%. | New England Journal of Medicine 2021 ↗ |
| [2]STEP 2 | 9.6% mean weight loss — lower than STEP 1 because type 2 diabetes reduces GLP-1 response. Significant HbA1c improvements. | New England Journal of Medicine 2021 ↗ |
| [3]STEP 5 | 15.2% sustained mean weight loss at 2 years — showing durable effect with continued use. | Nature Medicine 2022 ↗ |
| [4]OASIS 4 (oral semaglutide 25mg) | 13.6% average weight loss (all participants, including those who reduced dose or stopped). 16.6% average weight loss with full adherence. 76.3% achieved ≥5% weight loss vs. 31.3% placebo. About 1 in 3 adherent participants achieved ≥20% weight loss. | New England Journal of Medicine 2024 ↗ |
| [5]SELECT (cardiovascular outcomes) | 20% reduction in MACE (non-fatal heart attack, non-fatal stroke, or cardiovascular death) vs. placebo — the first weight loss drug to demonstrate CV event reduction. | New England Journal of Medicine 2023 ↗ |
| [6]Wegovy (semaglutide) tablets — FDA prescribing information | 6.9% of tablet-treated patients discontinued treatment due to adverse reactions, vs. 5.9% with placebo (section 6.1, adverse reactions). | FDA prescribing information (DailyMed) 2025 ↗ |
Reported side effects
The rates below come from the STEP 1 trial. View source
| Side effect | Frequency in trial |
|---|---|
| Nausea | 44% |
| Diarrhoea | 30% |
| Vomiting | 24% |
| Constipation | 24% |
Body composition data
DXA substudy data from STEP 1 showed semaglutide cut fat mass proportionally more than it cut lean mass. That is consistent with findings from other GLP-1 drugs. Lean mass loss was in proportion to the amount of weight lost overall.
Heart and metabolic data
The SELECT trial (n=17,604) showed a 20% reduction in major adverse cardiovascular events against placebo. Those events — heart attack, stroke or cardiovascular death — are together called MACE. The people in the trial were adults with obesity and established cardiovascular disease, without diabetes. STEP-HFpEF also showed fewer heart failure events.