Summary: In a patient-reported outcomes analysis pooling the four 68-week, double-blind STEP 1-4 trials of adults with overweight or obesity, once-weekly semaglutide 2.4 mg met its confirmatory secondary endpoint of physical functioning. A meaningful within-person change in IWQOL-Lite-CT Physical Function was reached by 51.8% on semaglutide versus 28.3% on placebo in STEP 1 (p<0.0001). Other quality-of-life domains were only numerically improved.
PICO Summary
| Element | Detail |
|---|---|
| Population | Adults with overweight or obesity enrolled in the STEP 1-4 Phase 3a randomized controlled trials; pooled patient-reported-outcome analysis over 68 weeks. Trial enrolment was international (multinational Phase 3a programme). |
| Intervention | Once-weekly subcutaneous semaglutide 2.4 mg plus lifestyle support, assessed by change from baseline to Week 68 on IWQOL-Lite-CT (STEP 1 and 2) and SF-36v2 (STEP 1-4). |
| Comparison | Once-weekly placebo plus lifestyle support over the same 68 weeks, within each randomized trial. |
| Outcome | Superiority for physical functioning was confirmed for semaglutide versus placebo on IWQOL-Lite-CT (STEP 1 and 2) and SF-36v2 (STEP 1, 2 and 4). Meaningful within-person change on IWQOL-Lite-CT Physical Function: STEP 1 51.8% vs 28.3% (p<0.0001); STEP 2 39.6% vs 29.5% (p=0.0083). Meaningful within-person change on SF-36v2 Physical Functioning: STEP 1 39.8% vs 24.1% (p<0.0001); STEP 2 41.0% vs 27.3% (p=0.0005); STEP 4 18.0% vs 6.6% (p<0.0001). All other IWQOL-Lite-CT and SF-36v2 scales were numerically improved with semaglutide except SF-36v2 Role Emotional in STEP 2. Confidence intervals, absolute risk reduction and number needed to treat were not reported in the abstract. |
Semaglutide 2.4 mg and physical functioning
Pooled PRO analysis · overweight or obesity · 68 weeks
In STEP 1, 51.8% of patients on semaglutide 2.4 mg reached a meaningful within-person improvement in physical function versus 28.3% on placebo, a statistically robust patient-reported benefit alongside weight loss.
Expert Commentary
This pooled patient-reported-outcomes analysis adds a credible patient-centred dimension to the STEP weight-loss programme. The confirmatory secondary endpoint of physical functioning was met, and the responder analyses are internally consistent: across STEP 1, 2 and 4, more participants on semaglutide 2.4 mg reached a meaningful within-person change in physical function than on placebo, with effects that are statistically robust rather than marginal. The verdict is that semaglutide produces a genuine, measurable improvement in how patients experience their physical capacity, not merely a number on the scale. The principal limitation is that only physical functioning was a confirmatory endpoint; the remaining IWQOL-Lite-CT and SF-36v2 domains were numerically better but not formally confirmed, so they should be read as supportive, not proven. The trials were manufacturer-sponsored (Novo Nordisk) with several author affiliations to the sponsor, which warrants the usual caution, though the double-blind randomized design and pre-specified responder thresholds mitigate bias. Can I use this with my patients? Yes, for adults with overweight or obesity who are candidates for semaglutide 2.4 mg, this supports counselling that meaningful gains in physical function are plausible alongside weight loss. Clinicians should set expectations around physical function specifically and reassess quality of life directly at follow-up.
References
Rubino D, Bjorner JB, Rathor N, Sharma AM, von Huth Smith L, Wharton S, et al. Effect of semaglutide 2.4 mg on physical functioning and weight- and health-related quality of life in adults with overweight or obesity: patient-reported outcomes from the STEP 1-4 trials. Diabetes Obes Metab. 2024;26(7):2945-2955. doi:10.1111/dom.15620