β3-Adrenoceptor Agonists for Neurogenic Lower Urinary Tract Dysfunction: Evidence and Clinical Rationale for First-Line Therapy.

Abstract

Aims: To summarize current evidence on β3-adrenoceptor agonists for managing neurogenic lower urinary tract dysfunction (NLUTD), focusing on their efficacy, safety, and clinical role in optimizing bladder storage and protecting upper tracts.

Methods: Evidence from randomized controlled trials, meta-analyses, and observational studies in spinal cord injury (SCI), multiple sclerosis (MS), and spina bifida populations was reviewed. Outcomes included bladder storage parameters, patient-reported measures, and cardiovascular and cognitive safety profiles.

Results: β3-adrenoceptor agonists such as Mirabegron improve cystometric capacity, reduce detrusor pressure, and enhance quality of life. A recent individual-patient meta-analysis confirmed these benefits. Early data on Vibegron in SCI and spina bifida show increased bladder compliance and capacity without new safety concerns. Cardiovascular safety signals are reassuring: one randomized trial in SCI/MS and a large multinational cohort both showed no excess risk. Observational studies continue to associate antimuscarinics with cognitive adverse effects, whereas β3-agonists demonstrate a more favorable tolerability profile.

Conclusions: β3-adrenoceptor agonists represent a safe, effective, and well-tolerated first-line option in NLUTD management. They preserve bladder safety and continence with fewer systemic side effects. OnabotulinumtoxinA remains an important escalation therapy for refractory cases but carries higher procedural and retention risks. A β3-agonist-based strategy offers a rational, patient-centered foundation for treatment.