Summary: In adults with obesity and prediabetes, once-weekly semaglutide 2.4 mg reduced bodyweight by 13.9% versus 2.7% with placebo at 52 weeks (estimated treatment difference -11.2%; 95% CI -13.0 to -9.4; p<0.0001). Reversion to normoglycaemia was reached by 81% versus 14% (odds ratio 19.8; 95% CI 8.7 to 45.2; p<0.0001) in this manufacturer-funded, double-blind phase 3 trial.
PICO Summary
| Element | Detail |
|---|---|
| Population | 207 adults aged 18 years or older with obesity (mean BMI 40.1 kg/m²) and prediabetes by NICE criteria (HbA1c 6.0-6.4% or fasting plasma glucose 5.5-6.9 mmol/L); randomised, double-blind, parallel-group phase 3 trial across 30 sites in Canada, Denmark, Finland, Spain, and the UK (NCT05040971). |
| Intervention | Once-weekly subcutaneous semaglutide 2.4 mg plus diet and physical activity counselling for 52 weeks, followed by a 28-week off-treatment period (n=138). |
| Comparison | Matching placebo injections plus the same diet and physical activity counselling (n=69; 2:1 allocation). |
| Outcome | Bodyweight change at 52 weeks -13.9% (SD 0.7) versus -2.7% (SD 0.6); estimated treatment difference -11.2% (95% CI -13.0 to -9.4; p<0.0001). Reversion to normoglycaemia 103/127 (81%) versus 9/64 (14%); odds ratio 19.8 (95% CI 8.7 to 45.2; p<0.0001). Serious adverse events 9% in each group; discontinuation for adverse events 6% versus 1%; no new safety signals. |
Semaglutide 2.4 mg in obesity and prediabetes (STEP 10)
RCT · obesity + prediabetes · 52 weeks
Once-weekly semaglutide 2.4 mg cut bodyweight by 11.2 percentage points more than placebo and made reversion to normoglycaemia nearly 20-fold more likely at 52 weeks, though both were measured on treatment.
Expert Commentary
The verdict is that semaglutide 2.4 mg delivered a clear and clinically meaningful effect in this population, with both co-primary endpoints met and effect sizes that are consistent with the wider STEP programme. An 11.2 percentage-point separation in weight and an odds ratio near 20 for reversion to normoglycaemia are difficult to dismiss, and the safety profile was as expected for a GLP-1 receptor agonist. Two cautions temper the enthusiasm. The trial was funded by the manufacturer, several authors were employees, and the cohort was small (207 participants) and predominantly White (88%), which limits how far the glycaemic findings generalise. The single most weighed limitation, however, is the outcome itself: reversion to normoglycaemia is a biochemical surrogate measured on treatment, not a demonstration that progression to type 2 diabetes is prevented, and the 28-week off-treatment phase raises the familiar question of weight regain once the drug is stopped. Can I use this with my patients? Yes, for adults with class II to III obesity and prediabetes who are candidates for pharmacotherapy, with the honest caveat that durability beyond the treatment period is unproven. Clinicians should frame this as a tool to be sustained, not a short course, and longer follow-up reporting hard dysglycaemia outcomes would be welcome.
References
McGowan BM, Bruun JM, Capehorn M, Pedersen SD, Pietiläinen KH, Muniraju HAK, et al. Efficacy and safety of once-weekly semaglutide 2.4 mg versus placebo in people with obesity and prediabetes (STEP 10): a randomised, double-blind, placebo-controlled, multicentre phase 3 trial. Lancet Diabetes Endocrinol. 2024;12(9):631-642. doi:10.1016/S2213-8587(24)00182-7