Summary: In adults with obesity without diabetes, once-weekly semaglutide 7.2 mg produced greater weight loss than placebo at 72 weeks (-18.7% vs -3.9%; estimated treatment difference -14.8 percentage points, 95% CI -16.2 to -13.4; P<0.0001). Dysaesthesia and gastrointestinal adverse events were more common, and the trial did not test cardiovascular outcomes.
PICO Summary
| Element | Detail |
|---|---|
| Population | 1407 adults with BMI 30 kg/m2 or greater and no diabetes; phase 3b, double-blind, active-controlled and placebo-controlled RCT across 95 centres in 11 countries. |
| Intervention | Once-weekly subcutaneous semaglutide 7.2 mg plus lifestyle intervention (n=1005). |
| Comparison | Once-weekly semaglutide 2.4 mg (n=201) or placebo (n=201), with the same lifestyle intervention. |
| Outcome | Mean body-weight change at week 72 was -18.7% with semaglutide 7.2 mg versus -3.9% with placebo (ETD -14.8 points, 95% CI -16.2 to -13.4; P<0.0001) and -15.6% with semaglutide 2.4 mg (ETD -3.1 points, 95% CI -4.7 to -1.6; P<0.0001). |
Semaglutide 7.2 mg for Obesity (STEP UP)
Phase 3b RCT - obesity - 72 weeks
Semaglutide 7.2 mg reduced body weight more than placebo and more than semaglutide 2.4 mg in adults with obesity without diabetes, but adverse effects remained common.
Expert Commentary
STEP UP shows that pushing semaglutide beyond the approved 2.4 mg maintenance dose yields additional weight loss in obesity, but the gain is incremental rather than transformational. The placebo-controlled effect was large, and the head-to-head difference versus 2.4 mg was statistically convincing, which strengthens confidence that the higher dose itself matters. The trade-off is tolerability: gastrointestinal events remained common, and dysaesthesia was notably more frequent with 7.2 mg. Can I use this with my patients? Not routinely today, because 7.2 mg is not the standard approved maintenance dose in most markets. If this formulation becomes available, it could fit adults with severe obesity who have responded to semaglutide but still need more weight loss and can tolerate slower escalation and close adverse-effect review. The study excluded diabetes, so this result should not be extrapolated to glycaemic management, and it did not test cardiovascular outcomes, long-term maintenance after dose withdrawal, or comparative effectiveness against tirzepatide. Novo Nordisk funded the trial, which matters less than the blinded design but still warrants independent confirmation in broader practice. The next questions are persistence, cost-effectiveness, neuropathic symptom relevance, and whether the extra weight loss changes hard clinical outcomes.
References
Wharton S, Freitas P, Hjelmesaeth J, et al. Once-weekly semaglutide 7.2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial. Lancet Diabetes Endocrinol. 2025;13(11):949-963. doi:10.1016/S2213-8587(25)00226-8. PMID: 40961952.