Vibegron Outranks Mirabegron, Tolterodine on Several OAB Measures

Vibegron (Gemtesa; Sumitomo Pharma America) outranked mirabegron (Myrbetriq; Astellas Pharma US) and tolterodine (Detrol LA; Viatris) on urgency-related symptoms of overactive bladder (OAB) in an indirect comparison of phase 3 trials, but it also had the highest odds of any adverse event, according to a systematic review and network meta-analysis recently published in the European Journal of Obstetrics & Gynecology and Reproductive Biology.¹

Comparing OAB Pharmacotherapy Options

When lifestyle changes and bladder training fall short for patients with OAB, pharmacotherapy becomes the second-line option. Antimuscarinics, such as tolterodine, have long been the mainstay, but their anticholinergic effects, including dry mouth, constipation, and cognitive changes, contribute to high discontinuation rates.

Mirabegron, the first beta-3 adrenergic agonist for OAB, entered UK treatment pathways in 2013. Vibegron is a newer beta-3 adrenergic agonist option to treat OAB, receiving approval in Japan in 2018; it is dosed once daily without titration and does not require dose adjustment in patients with hepatic or renal dysfunction. The UK's National Institute for Health and Care Excellence has included vibegron in its OAB pathway since 2024. However, researchers noted that no adequately powered randomized trial has directly compared the 2 agents, leaving clinicians without robust comparative evidence.

To fill that gap, investigators searched MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov through May 2025 for phase 3, double-blind, parallel-group trials in adults with idiopathic OAB that evaluated vibegron 75 mg, mirabegron 50 mg, or tolterodine 4 mg once daily, or placebo. The primary end point was change from baseline in daily urinary urgency (UU) episodes. Secondary end points included urgency urinary incontinence (UUI), 24-hour micturition frequency, maximum voided volume (MVV), and adverse events. The researchers ranked treatments using surface under the cumulative ranking curve values.

Vibegron Leads on Several OAB Efficacy Measures

Of 2647 records screened, 5 multicenter trials with 12-week treatment periods met criteria, for a total of 5317 participants. Across these studies, all 3 active treatments reduced UU episodes compared with placebo. Vibegron showed the largest mean difference (MD; –0.66; 95% CI, –1.10 to –0.22), followed by mirabegron (–0.52; 95% CI, –0.76 to –0.27) and tolterodine (–0.38; 95% CI, –0.50 to –0.16).

Vibegron also ranked first for UUI (MD, –0.69; 95% CI, –1.01 to –0.37), with a significantly greater improvement than both mirabegron (MD, –0.36; 95% CI, –0.56 to –0.16) and tolterodine (MD, –0.29; 95% CI, –0.47 to –0.10). It also ranked first for MVV, with an MD of 21.04 mL (95% CI, 11.71-30.37) vs roughly 12 mL for both mirabegron and tolterodine.

The ranking reversed for urinary frequency, however. Mirabegron produced the largest reduction in daily micturitions (MD, –0.63; 95% CI, –0.82 to –0.44), a significantly greater improvement than vibegron (MD, –0.53; 95% CI, –0.85 to –0.22) and a numerical advantage over tolterodine (MD, –0.24; 95% CI, –0.41 to –0.07).

The safety profiles also varied across treatments. Vibegron had the highest odds of any adverse event (OR, 1.51; 95% CI, 1.08-2.10), followed by tolterodine (OR, 1.36; 95% CI, 1.09-1.70), while mirabegron's odds did not differ significantly from placebo (OR, 0.89; 95% CI, 0.69-1.15).

"These findings, combined with consideration of patient preferences, comorbidities, and cost, can help clinicians optimise individualised treatment strategies for patients suffering from OAB," the authors concluded.

Guidance Favors Beta-3 Agonists, but More Evidence Is Needed

The analysis comes as specialty guidance has shifted toward beta-3 agonists. The 2024 guideline from the American Urological Association and the Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction advised clinicians to discuss the potential risk of dementia and cognitive impairment with patients taking antimuscarinics.² It also stated that a trial of a beta-3 agonist is typically preferred before an antimuscarinic.

However, the authors acknowledged several limitations of the current study.¹ The network included only 5 trials, all with short-term follow-up. The trials also defined and reported adverse events inconsistently, meaning the safety findings were descriptive rather than definitive. Because of these limitations, the researchers called for further research.

“Future studies should prioritise direct, long-term, active-comparator [randomized controlled trials] between vibegron and mirabegron,” they wrote. “…Research should also explore predictors of response to different drug classes to allow for personalisation of treatment and individualised care. Further investigation into the real-world effectiveness, adherence, and health care costs associated with these newer agents is also required.”

References

1. Mohamed-Ahmed R, Rantell A, Robinson D. Comparing the safety and efficacy of vibegron, mirabegron and tolterodine in patients with overactive bladder: a systematic review and network meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2026;325:115321. doi:10.1016/j.ejogrb.2026.115321
2. Cameron AP, Chung DE, Dielubanza EJ, et al. The AUA/SUFU guideline on the diagnosis and treatment of idiopathic overactive bladder. J Urol. 2024;212(1):11-20. doi:10.1097/JU.0000000000003985