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4 Discussion Current evidence strongly supports the efficacy of GLP-1 receptor agonists for inducing substantial weight loss, improving metabolic control, and reducing cardiovascular risk often surpassing the short-term effects of exercise alone ( Exercise and lifestyle interventions, while generally less potent for weight loss, provide unique and irreplaceable health benefits preserving skeletal muscle, improving cardiorespiratory fitness, enhancing psychological well-being, and lowering chronic disease risk ( Hybrid care models that integrate pharmacotherapy with behavioral support are emerging as the most promising framework for sustainable obesity and diabetes management ( Persistent challenges include the high cost and limited accessibility of GLP-1RAs, variable long-term adherence, and a lack of long-term data on sustainability, relapse rates, and overall health outcomes

Methods Search Strategy and Study Selection The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was inspected for the systematic review ( Tables S1, S2 , respectively

We extracted 62 sphingolipids, 46 steroids, and 118 microbial-derived metabolites to replicate our findings in the MGBB-LLF cohort

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