Mirabegron versus Placebo and Other Therapeutic Modalities in the Treatment of Patients with Overactive Bladder Syndrome-A Systematic Review

Overactive Bladder (OAB) is a common condition characterised by sudden urinary urgency, often accompanied by increased daytime frequency and nocturia, with or without urinary incontinence. Its prevalence rises with age, affecting 7% to 27% of men and 9% to 43% of women over 40. Many individuals hesitate to seek medical help due to stigma or lack of awareness. The general risk factors include obesity, smoking, depression, and cardiovascular disease, while gender-specific risks include prostate disease in men and menopause, pregnancy, or neurological conditions in women.

Diagnosing OAB requires excluding infections and stress incontinence. For men, overlapping lower urinary tract symptoms (LUTS) add complexity, often necessitating urodynamic assessments. Beyond physical symptoms, OAB significantly reduces quality of life, contributing to anxiety, depression, and disrupted daily functioning. Its causes remain multifactorial, with theories involving neurogenic, myogenic, and signaling dysfunctions.

The European Association of Urology recommends a stepwise approach, starting with lifestyle changes like caffeine reduction, behavioural therapies, and non-pharmacological interventions. Antimuscarinics dominated drug therapy until 2013, when mirabegron, the first beta-3 adrenergic receptor agonist, transformed OAB management by offering effective symptom relief with fewer side effects. Beta-3 adrenoceptors, predominantly found on detrusor smooth muscle cells, induce relaxation when activated and are also present in suburothelial cholinergic nerve endings. This systematic review evaluates the efficacy and safety of mirabegron compared to other interventions, highlighting its pivotal role in advancing OAB care.

After comparing twenty clinical trials assessing mirabegron with placebo and anticholinergics, we identified that mirabegron is safe, effective, and well tolerated, especially when co-administered with anticholinergics, which returns an advantageous positive effect causing fewer adverse events.

This systematic review has identified significant improvements with Mirabegron 25/50 mg when comparing placebo within three months of treatment on micturition, urgency, urge urinary incontinence, total incontinence, and nocturia episodes per 24h assessments, including a higher effect on voided volume/micturition in ml and zero incontinence conditions. Mirabegron 50mg positively affected micturition, urgency, UUI, nocturia, total incontinence, and voided vol/mic in ml episodes, compared to imidafenacin 0.2m,g with an overall significant reduction in adverse events. A separate comparison with Mirabegron 25/50 mg demonstrated improving results on micturition, urgency, UUI, and total incontinence episodes with tolterodine 4mg within three months of treatment.

In comparison with oxybutynin 73.5mg, patients reported fewer adverse events with mirabegron 50 mg, showing a slight improvement in nocturia episodes. Many trials were conducted comparing mirabegron and solifenacin with some add-ons mirabegron + solifenacin vs solifenacin RCTs. Mirabegron 25/50mg depicted improving effects when compared with different solifenacin dosages of 2.5/5/10 mg, which includes common conditions such as micturition, urgency, UUI, total incontinence, and zero incontinence episodes. One of the strengths of this systematic review was also assessing the add-on benefits and safety within mirabegron plus solifenacin comparing the solifenacin monotherapy. Improving effects were specifically observed with mirabegron + solifenacin 2.5mg in micturition, urgency, nocturia, and voided volume/mic in ml comparing solifenacin 2.5mg, where participants’ discontinuation rates were less. There are more common adds-on benefits with mirabegron + solifenacin 5mg and mirabegron + solifenacin 10mg in UUI and total incontinence episodes, improving the voided volume/mic in ml conditions and causing fewer discontinuation/drop-out participants from the trials when compared with monotherapies of solifenacin 5mg and 10mg. Lastly, the additive effect of mirabegron 50 mg + solifenacin 5 mg clarified improvement in micturition, urgency, UUI, nocturia, and incontinence episodes with an overall reduction in AEs compared with solifenacin 10 mg.

This systematic review evaluated mirabegron, the first beta-3 agonist, alongside other pharmacological and non-pharmacological interventions for OAB, incorporating the most recent clinical trial evidence. Consistent with prior reviews, our findings confirm that mirabegron is an effective, safe, and well-tolerated option for OAB management. Additionally, combining mirabegron with anticholinergics enhances treatment efficacy without increasing side effects, offering a promising strategy for improved symptom control.

Vibegron, another beta-3 agonist, has shown promise but was outside the scope of this systematic review. Recently, three clinical trials assessed mirabegron and vibegron for their clinical safety and effectiveness. Kinjo et al., in a study of 199 patients, found no significant difference between mirabegron and vibegron in OAB symptom improvement.¹ Both drugs significantly reduced micturition frequency, urgency episodes, and UUI, with slight, nonsignificant increases in voided volume (mirabegron: 185.69 mL; vibegron: 197.76 mL) over 12 weeks. Adverse event rates were comparable (mirabegron: 17.5%; vibegron: 15.7%), and both interventions improved OABSS, quality of life, and voiding diary outcomes in postmenopausal women.

In Wada et al.'s RCT comparing 40 mirabegron and 43 vibegron patients, both drugs demonstrated similar efficacy in improving OAB symptoms. Vibegron showed slightly greater reductions in OABSS, nocturia, urgency, and urgency incontinence, with a modest increase in voided volume (40 mL vs. 34 mL). Adverse events were comparable (8.3% for mirabegron; 6.3% for vibegron). Patient preferences leaned toward vibegron (53%), while 27% favoured mirabegron, and 20% had no preference, supporting both as effective options for female patients with OAB.

Sato et al.'s RCT involving 104 patients compared oral mirabegron 50 mg and vibegron 50 mg over 12 weeks. Both drugs showed similar improvements in Overactive bladder symptoms score (OABSS), nocturia, and urgency episodes. However, vibegron had a higher rate of overall adverse events (38.5% vs. 19.1%) and serious adverse events (five patients vs. one with mirabegron). The study concluded that both medications effectively improved OAB symptoms, with mirabegron demonstrating a better safety profile.

This systematic review highlights mirabegron as a highly effective, safe, and well-tolerated intervention for managing OAB symptoms. Additionally, combining mirabegron with anticholinergics enhances therapeutic outcomes, offering improved symptom control without significantly increasing the risk of side effects. This dual approach provides a valuable option for patients requiring more comprehensive management of OAB.

Written by:

Anirban Dey, Academic Urology Unit, University of Aberdeen, Aberdeen, UK
Georgios Georgiadis, Department of Urology, University General Hospital of Heraklion, University of Crete, Medical School, Heraklion, Crete, Greece
Justin Umezurike, Academic Urology Unit, University of Aberdeen, Aberdeen, UK
Yuhong Yuan, Department of Medicine, London Health Science Centre, London, Ontario, Canada
Fawzy Farag, Department of Urology, Sohag University Hospital, Sohag, Egypt
James N'Dow, Academic Urology Unit, University of Aberdeen, Aberdeen, UK
Muhammad Imran Omar, Academic Urology Unit, University of Aberdeen, Aberdeen, UK; Guidelines Office, European Association of Urology, Arnhem, The Netherlands
Charalampos Mamoulakis, Department of Urology, University General Hospital of Heraklion, University of Crete, Medical School, Heraklion, Crete, Greece

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