Summary: In the manufacturer-sponsored STEP 10 phase 3 trial, 207 adults with obesity and prediabetes were randomised 2:1 to once-weekly semaglutide 2.4 mg or placebo, each with lifestyle counselling, for 52 weeks. Semaglutide produced a far greater reduction in bodyweight (-13.9% vs -2.7%; estimated treatment difference -11.2%) and a much higher rate of reversion to normoglycaemia (81% vs 14%; odds ratio 19.8).
PICO Summary
| Element | Detail |
|---|---|
| Population | 207 adults aged 18 years or older with obesity (BMI ≥30 kg/m²; baseline mean BMI 40.1) and prediabetes by UK NICE criteria (HbA1c 6.0-6.4% or fasting plasma glucose 5.5-6.9 mmol/L). Randomised, double-blind, placebo-controlled phase 3 trial across 30 sites in Canada, Denmark, Finland, Spain, and the UK. |
| Intervention | Once-weekly subcutaneous semaglutide 2.4 mg plus diet and physical activity counselling for 52 weeks (n=138). |
| Comparison | Placebo plus the same diet and physical activity counselling for 52 weeks (n=69). |
| Outcome | Bodyweight change at week 52: -13.9% (SD 0.7) vs -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%) vs 9/64 (14%); odds ratio 19.8 (95% CI 8.7 to 45.2; p<0.0001). Serious adverse events 9% in both groups; discontinuation due to adverse events 6% (semaglutide) vs 1% (placebo). No new safety signals. |
STEP 10: semaglutide 2.4 mg in obesity and prediabetes
RCT · obesity + prediabetes · 52 weeks
Semaglutide 2.4 mg cut bodyweight by 13.9% versus 2.7% with placebo and drove reversion to normoglycaemia in 81% versus 14%, both highly significant at 52 weeks.
Expert Commentary
STEP 10 delivers a clear, internally consistent verdict: in adults with obesity and prediabetes, once-weekly semaglutide 2.4 mg was superior to placebo for both weight loss and reversion to normoglycaemia, with effect sizes that are large but in keeping with what has been observed across the semaglutide obesity programme. The double-blind design and intention-to-treat analysis lend the headline figures credibility, and the safety profile was unremarkable for the GLP-1 receptor agonist class. The principal limitation is durability. The primary endpoints were assessed at 52 weeks while participants remained on treatment, and the planned 28-week off-treatment period is where the harder question lies, because weight regain and glycaemic relapse after GLP-1 receptor agonist withdrawal have been documented elsewhere; reversion to normoglycaemia on drug should not be read as cure. It should also be noted that the trial was funded by Novo Nordisk, the manufacturer, and that the population was modest in size and predominantly White. Can I use this with my patients? Yes, for the adult with obesity and prediabetes in whom intensified weight management is appropriate and access permits, this strengthens the case for semaglutide 2.4 mg as a means of lowering glycaemic risk, provided expectations about post-treatment relapse are set honestly. Reporting of the off-treatment follow-up is awaited to clarify whether benefit is sustained.
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
