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

Abstract

This nonsystematic review provides a summary of current evidence on the use of β 3 -adrenoreceptor agonists (β 3 -ARAs) for the treatment for lower urinary tract symptoms. Soon after their discovery in 1989, β 3 -ARs were identified as a predominant adrenoreceptor subtype in the human urinary bladder. Although it is widely believed that β 3 -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 β 3 -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 β 3 -ARAs are being developed; however, to date none has been introduced to clinical use. All β 3 -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 β 3 -ARAs with anticholinergic compounds allows for increased efficacy.

Beta-blockers in patients with liver cirrhosis: Pragmatism or perfection?

“…For instance, 10.3389/fmed.2022.1100966 ß 1 -AR of the kidney are involved in renin secretion, whereas ß 2 -AR directly influence sodium concentration in the tubular system via ion channels/transporters (32). ß 3 -AR are expressed in a variety of human tissues such as skeletal muscle, atrium, heart, adipose tissue, brain or-to a great extent-in the urinary bladder (33)(34)(35). We found an up-regulated expression of ß 3 -AR in arteries and the liver in the condition of liver cirrhosis (36).…”

Mirabegron Add-On Tamsulosin for Men with Overactive Bladder Symptoms: A Pooled Analysis of Four Randomized Controlled Trials

“…In the management of patients with OABS, mirabegron is being gradually substituted for antimuscarinic agents because of its curative effect similar to that of antimuscarinic medications and fewer treatment-emergent adverse events (TEAEs), especially in elderly men [9]. β3-AR agonists combined with anticholinergics or α1Bs were reported to be more effective than monotherapy due to differences in the mechanism of action between drugs used alone and in combination [10]. Several studies have analyzed the efficacy and safety of mirabegron add-on therapy to tamsulosin in patients with OABS [11][12][13][14].…”