A Systematic Review and Meta‐Analysis of Semaglutide Effects on Adipose Tissue and Emerging Effects on Brain and Cognition

BACKGROUND: In 2023 and 2024, research into semaglutide (SEMA), an antiobesity and antidiabetic medication, indicated potential benefits beyond its approved uses, particularly in preventing Alzheimer's disease (AD). This highlights the link between obesity and AD development. OBJECTIVES: This systematic review and meta-analysis evaluates clinical studies assessing SEMA's effects on subcutaneous and visceral adipose tissue (SAT/VAT) measures, brain function, cognitive performance through cognitive tasks, and the incidence of cognitive disorders. METHODS: We searched databases for studies evaluating these outcomes pre- and post-SEMA treatment, with the last update on November 9, 2024. We included studies regardless of treatment duration, estimating pre-post standardized mean differences (SMD) for one-group and two-group designs using a random-effects model. RESULTS: We included 23 studies: 18 on SAT/VAT outcomes and five on brain function and cognitive impairment. Meta-analyses revealed significant VAT reductions but no significant impact on SAT. SEMA demonstrated neuroprotective effects, lowering the risk of AD compared to various treatments. CONCLUSION: Our systematic appraisal highlighted high heterogeneity across available original investigations. Within this context, meta-analytic findings suggest that SEMA may be able to promote VAT loss and support cognitive preservation. Sequencing these effects, VAT loss and cognitive preservation, is an important question open for further exploration.