Lemborexant Linked to Lower Hip Fracture Risk Than Z-Drugs in Older Adults

A cohort study published in the Journal of the American Geriatrics Society used databases from Tochigi Prefecture, Japan, to emulate a target trial comparing lemborexant and suvorexant with Z-drugs in adults aged ≥65 years newly initiating treatment. The primary outcome was hospitalization for hip fracture within one year. Investigators estimated per-protocol effects of continuous treatment, using inverse probability weights to adjust for baseline confounding and censoring after treatment discontinuation or switching to the comparator.

The lemborexant cohort included 22,655 individuals: 6,879 receiving lemborexant and 15,776 receiving Z-drugs. Lemborexant was associated with lower hip fracture risk (adjusted HR 0.31, 95% CI 0.16–0.59; p<0.001). The suvorexant cohort included 22,377 individuals: 6,699 receiving suvorexant and 15,678 receiving Z-drugs. Its risk estimate was also lower, but the confidence interval included no difference (adjusted HR 0.57, 95% CI 0.23–1.44; p=0.234).

These findings may inform insomnia prescribing in older adults, particularly when fracture risk is a concern. However, the observational design cannot establish causality, and residual confounding remains possible despite adjustment. The abstract does not report absolute fracture risks, limiting assessment of absolute benefit. The results do not establish a class-wide safety advantage for dual orexin receptor antagonists.