AIMS: Semaglutide 2.4 mg causes substantial weight loss, but its average effect on patient-reported physical function requires interpretation against clinically meaningful thresholds and routine clinical expectations. This systematic review and meta-analysis aimed to evaluate the effects of once-weekly subcutaneous semaglutide 2.4 mg on patient-reported physical functioning and weight-related quality-of-life outcomes in adults with overweight or obesity.
MATERIALS AND METHODS: In this prospectively registered systematic review and meta-analysis, MEDLINE via PubMed, Embase via Elsevier Embase.com, Cochrane CENTRAL, Scopus, and ClinicalTrials.gov were searched for randomised placebo-controlled trials of once-weekly subcutaneous semaglutide 2.4 mg in adults with overweight or obesity reporting SF-36v2 or IWQOL-Lite-CT outcomes. Four STEP trials, including 4182 participants, contributed SF-36v2 Physical Functioning data.
RESULTS: Semaglutide improved SF-36v2 Physical Functioning compared with placebo, with a mean difference of 1.71 points and a 95% confidence interval of 1.07 to 2.35; heterogeneity was moderate, with I = 52.8%. However, this estimate was below the 3.7-point meaningful within-patient change threshold. Two trials, including 2768 participants, reported IWQOL-Lite-CT outcomes. Effects were larger in participants without type 2 diabetes and smaller in participants with type 2 diabetes, and both remained below published thresholds. 2
CONCLUSIONS: The available randomised evidence comes from the semaglutide development programme. Semaglutide statistically improves patient-reported outcomes, but average functional gains are modest and should be communicated cautiously.
