Huang Wenlin, Zheng Xueqin, Luo Jinyang, Chen Yongxiu, Xu Yong
Department of Urology, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, China.
Department of Gynecology, Louxing District People's Hospital, Loudi, China.
Eur J Clin Pharmacol. 2025 Jun 7. doi: 10.1007/s00228-025-03855-1.
To assess and compare the efficacy and adverse effects of β3-adrenergic receptor agonists (vibegron and mirabegron), alone and with antimuscarinic agents, in treating overactive bladder (OAB) via network meta-analysis (NMA) and component network meta-analysis (cNMA).
A search across multiple databases was done for Phase II/III RCTs from Jan. 2010 to June 2024. Adults with OAB or overactive bladder symptom score (OABSS) ≥ 3 were included. Trials evaluating vibegron (monotherapy/combination) and mirabegron combination therapies were eligible. Excluded were nonrandomized studies, secondary OAB, and long-term cardiovascular disease cases. Primary outcomes included micturition frequency (MF), urgency episodes (UE), urge urinary incontinence (UUI), and mean voided volume (MVV). Secondary outcomes were adverse events leading to treatment discontinuation (AELTD), adverse events (AEs), serious adverse events (sAEs), dry mouth, and constipation. Data analysis used the netmeta R package with both NMAs and cNMA.
Twelve studies (11,374 participants) were included. Vibegron outperformed mirabegron and antimuscarinics in reducing micturition frequency, with 100 mg vibegron showing the greatest reduction (SMD = - 0.87, 95% CI - 1.16 to - 0.59). Combination therapies generally had better efficacy in improving UE and UUI than monotherapies, except mirabegron 50 mg + tamsulosin. No significant MVV differences between treatments and controls. For AEs, there were no significant differences in overall AEs or AELTD between treatments and controls. But higher doses and combination therapies had higher risks of dry mouth and constipation. Component network meta-analysis (cNMA) showed greater reductions in micturition frequency, suggesting possible negative interactions, whereas standard NMA showed synergistic effects on urgency episodes (UE) and mean voided volume (MVV).
β3-agonists, especially vibegron, are effective for OAB symptoms (MF and UUI), both alone and with antimuscarinics. For short-term treatment, combination therapies seem superior to monotherapies in symptom control.
通过网络荟萃分析（NMA）和成分网络荟萃分析（cNMA）评估和比较β3肾上腺素能受体激动剂（维贝格隆和米拉贝隆）单独使用以及与抗毒蕈碱药物联合使用治疗膀胱过度活动症（OAB）的疗效和不良反应。
检索多个数据库，查找2010年1月至2024年6月期间的II/III期随机对照试验。纳入患有OAB或膀胱过度活动症状评分（OABSS）≥3的成年人。评估维贝格隆（单药治疗/联合治疗）和米拉贝隆联合治疗的试验符合条件。排除非随机研究、继发性OAB和长期心血管疾病病例。主要结局包括排尿频率（MF）、尿急发作次数（UE）、急迫性尿失禁（UUI）和平均排尿量（MVV）。次要结局是导致治疗中断的不良事件（AELTD）、不良事件（AE）、严重不良事件（sAE）、口干和便秘。数据分析使用netmeta R包进行NMA和cNMA。
纳入12项研究（11374名参与者）。在降低排尿频率方面，维贝格隆优于米拉贝隆和抗毒蕈碱药物，100mg维贝格隆降低幅度最大（标准化均值差[SMD]= -0.87，95%可信区间[-1.16至-0.59]）。除50mg米拉贝隆+坦索罗辛外，联合治疗在改善UE和UUI方面通常比单药治疗疗效更好。治疗组与对照组之间MVV无显著差异。对于AE，治疗组与对照组之间总体AE或AELTD无显著差异。但较高剂量和联合治疗口干和便秘风险更高。成分网络荟萃分析（cNMA）显示排尿频率降低幅度更大，提示可能存在负性相互作用，而标准NMA显示对尿急发作次数（UE）和平均排尿量（MVV）有协同作用。
β3激动剂，尤其是维贝格隆，单独使用或与抗毒蕈碱药物联合使用对OAB症状（MF和UUI）均有效。对于短期治疗，联合治疗在症状控制方面似乎优于单药治疗。
