Clinical Utility of β₃-Adrenoreceptor Agonists for the Treatment of Overactive Bladder: A Review of the Evidence and Current Recommendations

This nonsystematic review provides a summary of current evidence on the use of β₃-adrenoreceptor agonists (β₃-ARAs) for the treatment for lower urinary tract symptoms. Soon after their discovery in 1989, β₃-ARs were identified as a predominant adrenoreceptor subtype in the human urinary bladder. Although it is widely believed that β₃-ARAs cause detrusor relaxation, the effect on bladder afferent signaling likely plays an important role in their mechanism of action as well. In 2011 and 2012, mirabegron was approved for clinical use in overactive bladder (OAB) patients. Pooled analysis of data from prospective randomized studies on >60,000 OAB patients showed that when compared to placebo, mirabegron was superior with respect to reducing the frequency, number, and severity of urgency episodes, number of incontinence episodes and increasing dry rate, but not in reduction of nocturia episodes. The only side effect showing significantly higher incidence than placebo was nasopharyngitis. Mirabegron is approved for OAB treatment in all age-groups and in pediatric patients with neurogenic bladder. Vibegron is another β₃-ARA approved for OAB treatment in the US and Japan. Several large, multicenter, double-blind, randomized trials have documented statistically significant superiority of vibegron over placebo on all efficacy end points. Other β₃-ARAs are being developed; however, to date none has been introduced to clinical use. All β₃-ARAs provide efficacy similar to anticholinergics. They have a favorable safety profile and are well tolerated. Due to their different mechanisms of action, combination of β₃-ARAs with anticholinergic compounds allows for increased efficacy.