Semaglutide 2.4 mg statistically improves physical function and weight-related quality of life, but average gains are modest

Obesity and type 2 diabetes mellitus (T2DM) are prevalent chronic conditions significantly impacting patient quality of life (QoL) and increasing cardiometabolic risks. While semaglutide is known for its substantial weight loss effects, understanding its impact on patient-reported physical function and overall weight-related QoL is crucial for clinical practice. Current lifestyle interventions and even bariatric surgery sometimes fall short in addressing the multifaceted QoL impairments associated with obesity, highlighting the need for pharmacological agents that offer comprehensive benefits. This review addresses the gap in quantifying the clinically meaningful QoL improvements from semaglutide.

This systematic review and meta-analysis synthesized data from randomized placebo-controlled trials (RCTs) evaluating once-weekly subcutaneous semaglutide 2.4 mg in adults with overweight or obesity. Researchers searched MEDLINE, Embase, Cochrane CENTRAL, Scopus, and ClinicalTrials.gov for studies reporting SF-36v2 or IWQOL-Lite-CT outcomes. Four STEP trials, encompassing 4182 participants, contributed SF-36v2 Physical Functioning data. Two trials, with 2768 participants, reported IWQOL-Lite-CT outcomes, comparing semaglutide to placebo.

Semaglutide significantly improved SF-36v2 Physical Functioning compared to placebo, showing a mean difference of 1.71 points (95% confidence interval: 1.07 to 2.35). However, this average improvement was below the established 3.7-point threshold for a clinically meaningful within-patient change. Moderate heterogeneity was observed across studies, with an I2 value of 52.8%. For IWQOL-Lite-CT outcomes, effects were generally larger in participants without type 2 diabetes but smaller in those with type 2 diabetes. Crucially, improvements in IWQOL-Lite-CT scores in both groups also remained below published thresholds for clinical significance.