Lorcaserin reduces weight and fat mass, alters lipidomics in 48 adults with obesity over 6 months

BACKGROUND: Effective anti-obesity interventions that preserve lean mass are of increasing clinical significance for optimizing metabolic health. This study investigated whether lorcaserin, a centrally acting weight loss agent, modifies body composition, circulating lipidomic profiles, and muscle-regulating hormones within the myostatin-activin-follistatin-IGF-1 (MAFI) axes. METHODS: Forty-eight adults with obesity were randomized to lorcaserin (10 mg twice daily) or placebo for 6 months in a double-blind trial. Regional body composition, hormones and lipidomics were assessed. Changes were analysed using linear mixed models with fixed effects for time, treatment and interaction. Adjusted deltas and endpoints were compared by analysis of covariance controlling for baseline body mass index. Lipidomic profiles were analysed using principal component and partial least-squares discriminant analyses. RESULTS: Lorcaserin reduced total body weight (time*treatment, p = 0.004). Adjusted delta and endpoint comparisons showed reductions in total body (p = 0.031) and abdominal fat mass (p = 0.002). Lipidomic assessments revealed primarily lower levels of triglyceride-rich lipoproteins with treatment. No significant changes in MAFI axes components were detected in linear mixed models. CONCLUSIONS: Lorcaserin treatment was associated with greater abdominal fat mass loss, favourable lipid profile changes, while MAFI components remained largely unaffected. Lorcaserin may improve cardiometabolic health primarily through reductions in central adiposity.