<![CDATA[Chronic insomnia is a common sleep disorder that erodes quality of life, cognitive performance, and day-to-day safety. Benzodiazepines remain a mainstay of pharmacological treatment, yet their safety profile is a persistent concern, especially among older adults. Lemborexant, a newer dual orexin receptor antagonist, offers a distinct mechanism and a claim of improved safety. This review set out to weigh the two agents against each other on effectiveness and safety, focusing on daytime somnolence, fall risk, and cognitive impairment. A systematic review and meta-analysis was performed in line with the PRISMA 2020 guideline. Five databases (PubMed/MEDLINE, Scopus, EMBASE, the Cochrane Library, and ScienceDirect) were searched up to April 2026. Randomised controlled trials and comparative observational studies contrasting lemborexant with benzodiazepines or placebo in adults with insomnia were eligible. Risk of bias was appraised with the Cochrane RoB 2.0 tool and the Newcastle-Ottawa Scale. From 747 records, 18 studies entered the qualitative synthesis and 12 the quantitative analysis (n = 49,907 participants). Compared with benzodiazepines, lemborexant produced less daytime somnolence (SMD = -0.34; 95% CI: -0.52 to -0.16; p < 0.001), a lower risk of falls (log OR = -0.51; 95% CI: -0.72 to -0.30; p < 0.001), and less cognitive impairment (SMD = -0.18; 95% CI: -0.34 to -0.02; p = 0.028). Between-study heterogeneity was moderate (I² = 38-51%). Lemborexant shows a more favourable safety profile than benzodiazepines for daytime somnolence, falls, and cognition, particularly in older adults. The findings support considering lemborexant as a first-line pharmacological option for chronic insomnia when non-pharmacological therapy is unavailable or inadequate.]]>
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