Mirabegron Not Tied to Higher Obesity-Related Neoplasm Risk in OAB

Initiating mirabegron (Myrbetriq; Astellas Pharma) was not associated with a higher risk of obesity-related neoplasms than starting an antimuscarinic among patients with overactive bladder (OAB), according to a multicenter target trial emulation published in Cancers.¹ The analysis did identify a modestly higher risk of all-cause mortality with mirabegron, a finding the investigators called hypothesis-generating.

Prior Evidence on Mirabegron and Cancer Is Mixed

Mirabegron is a selective β3-adrenergic receptor agonist that can promote adipose tissue browning and alter systemic metabolism, raising interest in a possible link to cancer. Preclinical findings have been inconsistent. Neoplasms were reported more often among mirabegron recipients in some randomized development programs, while a post-authorization safety study found no increase in overall cancer risk, according to the paper. A Korean cohort study of more than 1.4 million patients with OAB reported higher kidney cancer incidence with mirabegron than with anticholinergics.²

Investigators used electronic health record data from the TriNetX Global Collaborative Network for a target trial emulation, an observational approach that mimics a randomized trial.¹ They compared adults 20 years or older with OAB or related lower urinary tract symptoms who newly initiated mirabegron or an antimuscarinic between 2013 and 2025, excluding those with a prior neoplasm. A 365-day lag period excluded patients with a recorded neoplasm or death in the first year, so follow-up began on day 366. Patients were analyzed by initial treatment regardless of later switching. Matching yielded 106,500 patients per group, with a mean age of about 63 years and roughly 73% women.

No Difference in Overall Neoplasm Risk

The composite outcome, which included benign cerebral meningioma, occurred in 2046 mirabegron initiators and 2803 antimuscarinic initiators (HR, 1.011; 95% CI, 0.954-1.071). None of the 12 site-specific neoplasm outcomes differed significantly between groups, including after Benjamini-Hochberg false discovery rate adjustment. Point estimates for kidney cancer (HR, 1.190; 95% CI, 0.969-1.462) and esophageal cancer (HR, 1.500; 95% CI, 0.972-2.316) were higher with mirabegron, but the intervals included 1.0. The investigators cautioned that the wide intervals do not rule out increased renal cell carcinoma risk and that null findings do not show equivalence.

At 3 years, the composite hazard ratio was 0.924 (95% CI, 0.859-0.994), a modestly lower risk with mirabegron. That association was not present at 5 years (HR, 0.975; 95% CI, 0.915-1.040) or over full follow-up, which the investigators said suggests the comparison may vary over time. A negative-control analysis of Hodgkin lymphoma, an outcome not expected to be affected by treatment, also showed no significant association.

Higher Mortality Signal Warrants Caution

Among patients who survived, remained free of neoplasms, and were observed through the first year, mirabegron initiation was associated with higher subsequent all-cause mortality (HR, 1.083; 95% CI, 1.044-1.124). Raw deaths were 5059 with mirabegron and 6816 with antimuscarinics, but mean follow-up was longer in the antimuscarinic group (1578 vs 1229 days).

The investigators noted that preferential prescribing to more vulnerable patients could contribute, as frailty is not fully captured despite well-balanced comorbidities. Because only first-year survivors were included, the estimate does not reflect mortality among all new users.

Authors Advise Against Changing Prescribing

The absence of an overall neoplasm association offers limited reassurance but does not establish long-term safety, according to the paper.

"The mortality signals alone should not prompt routine discontinuation or preferential antimuscarinic prescribing," the investigators wrote. Treatment decisions should remain individualized according to symptom burden, response, cognitive vulnerability, cardiovascular status, concomitant medications, affordability, and patient preferences. Additional endoscopic screening solely because of mirabegron exposure is not justified by these findings.

Limitations include residual confounding, reliance on diagnostic codes without pathology confirmation, incomplete body mass index and hemoglobin A1_c data, no formal competing-risk analysis, and unconfirmed medication dispensing or adherence. The study had no untreated comparator. The findings require prospective confirmation, and replication with absolute risk data and detailed frailty assessment is needed before clinical recommendations change, the paper stated.

References

1. Yen FS, Wei JCC, Hsu CC, et al. Comparative neoplasm risk of mirabegron and antimuscarinic therapy in overactive bladder: a multicenter target trial emulation. Cancers. 2026;18(20):3279. doi:10.3390/cancers18203279
2. Park JS, Choi SB, Kim J, Jang WS, Ham WS. Impact of β-adrenergic receptor agonist on kidney cancer risk in patients with overactive bladder. BJU Int. 2025;136(3):439-446. doi:10.1111/bju.16771