Editorial Comment to Efficacy of mirabegron, a β3‐adrenoreceptor agonist, in Japanese women with overactive bladder and either urgency urinary incontinence or mixed urinary incontinence: Post‐hoc analysis of pooled data from two randomized, placebo‐controlled, double‐blind studies

β3-adrenoreceptors (ARs) have been reported to play a major role in relaxation of the human bladder, and mirabegron is the first β3-AR agonist approved for the treatment of overactive bladder (OAB), including urgency urinary incontinence (UUI). In the present study, a post hoc analysis of pooled data from two randomized, placebo-controlled, double-blind studies, Takahashi et al.1 concluded that mirabegron is effective in patients with "OAB-wet", including those with UUI or mixed urinary incontinence (MUI). The two randomized studies included women predominantly (approximately 80%), therefore, evidence in men with OAB/benign prostatic hyperplasia is still required.2 This study reports the effects of mirabegron for MUI. However, the results did not show a direct effect of mirabegron on stress urinary incontinence (SUI). In a real-world clinical setting, anticholinergics and β3-agonists may be used for SUI-dominant MUI, or even pure SUI patients, possibly because there are no drugs for SUI other than clenbuterol. Some studies have reported the effects of anticholinergic drugs in SUI patients. For example, propiverine was reported to increase urethral pressure and suggested to be an effective treatment for the SUI component of MUI.3 It is not known whether other anticholinergic drugs could be effective in SUI. Previously, clenbuterol, a β2-AR agonist has been reported to enhance the contractility of the fast-contracting (type 2) fibers of the urethra, and thus to be effective in the treatment of SUI.4 The presence of the β3-AR had not been identified when this drug was launched in 1994. Thus, it is not known whether clenbuterol is a pure β2-AR-selective agonist, or whether it has some activity for β3-AR. Yamanishi et al.5 reported that β3-ARs are predominantly present in the bladder and urethra, and mediate relaxation of the detrusor and urethra in vitro. Those authors suggested that β3-ARs predominantly mediated relaxation, and that β2-ARs also played a role in relaxation of the urethra. Further study is recommended on the role of β3-AR agonists in the treatment of SUI. None declared.