Mirabegron

Mirabegron is a selective beta-3 adrenergic agonist medication primarily used to treat overactive bladder (OAB) in adults, characterized by symptoms such as urgency, urinary frequency, and urge incontinence.^[1] It is marketed under the brand name Myrbetriq and is available as extended-release oral tablets in 25 mg and 50 mg strengths, as well as an oral suspension for pediatric use.^[2] Approved by the U.S. Food and Drug Administration (FDA) in June 2012, mirabegron represents a non-antimuscarinic option for OAB management, offering an alternative to traditional therapies that often cause anticholinergic side effects.^[3] The drug functions by selectively activating beta-3 adrenoceptors in the bladder detrusor muscle, which leads to relaxation of the smooth muscle and increased bladder capacity during the storage phase of micturition.^[3] This mechanism enhances urine storage without significantly affecting bladder contraction during voiding, thereby alleviating OAB symptoms.^[2] Mirabegron can be administered alone or in combination with solifenacin succinate, another OAB treatment, to further improve efficacy in patients with persistent symptoms.^[1] Typical dosing for adults starts at 25 mg once daily, with potential escalation to 50 mg after 4 to 8 weeks based on response and tolerability; in patients with severe renal impairment or moderate hepatic impairment, the starting dose remains at 25 mg without increase.^[3] In addition to adult OAB, mirabegron is indicated for neurogenic detrusor overactivity (NDO) in pediatric patients aged 3 years and older weighing at least 35 kg, addressing urinary symptoms associated with neurological conditions.^[2] Common adverse effects include hypertension, nasopharyngitis, urinary tract infections, headache, and tachycardia, with blood pressure monitoring recommended due to potential increases in systolic and diastolic pressure.^[3] Contraindications include hypersensitivity to the drug; use is not recommended in patients with severe uncontrolled hypertension, while caution is advised in patients with bladder outlet obstruction to avoid urinary retention.^[2] Overall, mirabegron provides a well-tolerated profile compared to antimuscarinics, contributing to improved quality of life in OAB patients through reduced symptom burden.^[3]

Medical uses

Indications

Mirabegron is primarily indicated for the treatment of overactive bladder (OAB) in adults, specifically to reduce symptoms including urgency, urinary frequency, and urge urinary incontinence.^[4] This approval was granted by the U.S. Food and Drug Administration (FDA) in 2012 based on phase III clinical trials demonstrating significant improvements in these symptoms compared to placebo.^[3] It is also approved for the treatment of neurogenic detrusor overactivity (NDO) in pediatric patients aged 3 years and older, with FDA approval for this indication in 2021.^[5] This expansion addresses a need for non-invasive options in children with underlying neurological conditions contributing to bladder dysfunction. For patients weighing less than 35 kg, Myrbetriq Granules are used; for those 35 kg or more, either tablets or granules may be used. Clinical trials have established mirabegron's efficacy as comparable to antimuscarinics such as solifenacin in reducing mean micturition episodes per day and incontinence events, with phase III studies showing no statistically significant differences between mirabegron 50 mg and solifenacin 5 mg over 12 weeks.^[6] It is particularly preferred in patients intolerant to antimuscarinics due to its lower risk of cognitive side effects, as it lacks anticholinergic properties that can impair memory and attention in vulnerable populations.^[3] In some clinical guidelines, such as those from the UK National Institute for Health and Care Excellence (NICE), mirabegron is positioned as a second-line therapy after first-line antimuscarinics like oxybutynin, primarily due to considerations of cost-effectiveness rather than superior efficacy.^[7]

Administration and dosage

Mirabegron is formulated as extended-release oral tablets available in 25 mg and 50 mg strengths, as well as an extended-release oral suspension (8 mg/mL after reconstitution) for pediatric use.^[8] In adults with overactive bladder (OAB), the recommended starting dosage is 25 mg once daily, administered orally with water and with or without food. Based on individual patient efficacy and tolerability, the dose may be increased to 50 mg once daily after 4 to 8 weeks. Tablets must be swallowed whole and should not be chewed, divided, or crushed.^[8] For pediatric patients aged 3 years and older with neurogenic detrusor overactivity (NDO), dosing is weight-based and administered once daily with food. Tablets (for ≥35 kg) or granules reconstituted into oral suspension (for all weights) must be swallowed whole without chewing, dividing, or crushing; the suspension should be prepared and taken within 1 hour, using an appropriate measuring device.^[8]^[5] The recommended dosages are as follows:

Body Weight Range	Formulation	Starting Dose	Maximum Dose (after 4-8 weeks)
11 kg to <22 kg	Granules	3 mL (24 mg)	6 mL (48 mg)
22 kg to <35 kg	Granules	4 mL (32 mg)	8 mL (64 mg)
≥35 kg	Tablets	25 mg	50 mg
≥35 kg	Granules	6 mL (48 mg)	10 mL (80 mg)

Dosage adjustments are required in patients with renal or hepatic impairment. In adults with severe renal impairment (creatinine clearance 15 mL/min to less than 30 mL/min) or moderate hepatic impairment (Child-Pugh class B), the maximum recommended dosage is 25 mg once daily. Mirabegron is not recommended for use in patients with end-stage renal disease (creatinine clearance less than 15 mL/min or on dialysis) or severe hepatic impairment (Child-Pugh class C). Similar dose reductions to the maximum of 25 mg (or weight-equivalent) apply in pediatric patients with these impairments, and it is not recommended in those with end-stage renal disease or severe hepatic impairment.^[8]^[4] For adults with refractory OAB, mirabegron is approved for use in combination with solifenacin succinate 5 mg once daily; the starting dose is mirabegron 25 mg plus solifenacin 5 mg, which may be increased to mirabegron 50 mg plus solifenacin 5 mg after 4 to 8 weeks based on tolerability.^[8] Mirabegron is indicated for long-term administration to manage the chronic nature of OAB and NDO, with no specified duration limit in the prescribing information. If a dose is missed and it has been less than 12 hours since the scheduled time, it should be taken as soon as possible; otherwise, skip the missed dose and resume the regular schedule.^[8]

Pharmacology

Mechanism of action

Mirabegron is a selective β3-adrenergic receptor agonist that primarily targets receptors in the detrusor muscle of the bladder.^[3] By binding to these receptors, mirabegron stimulates the sympathetic pathway, which promotes relaxation of the bladder's smooth muscle during the storage phase of micturition.^[10] This selectivity accounts for over 95% of β-adrenergic receptor mRNA expression in human bladder tissue, enabling targeted therapeutic effects without broadly impacting other adrenergic pathways.^[10] Upon activation of β3-adrenergic receptors, mirabegron increases intracellular levels of cyclic adenosine monophosphate (cAMP) through the activation of adenylyl cyclase.^[3] Elevated cAMP inhibits the release of acetylcholine from parasympathetic nerves and directly relaxes detrusor smooth muscle cells, enhancing bladder capacity and reducing urgency associated with overactive bladder (OAB).^[10] Importantly, this relaxation occurs selectively during the bladder-filling phase and does not impair detrusor contraction during the voiding phase, preserving normal micturition function.^[3] Mirabegron exhibits minimal affinity for β1- and β2-adrenergic receptors, distinguishing it from non-selective agonists that can stimulate cardiac β1 receptors and bronchial β2 receptors, potentially leading to tachycardia or bronchoconstriction.^[11] This high selectivity for β3 receptors results in reduced cardiovascular side effects at therapeutic doses, making it a safer option for patients intolerant to antimuscarinics.^[11] As the first clinically available β3-adrenergic agonist approved for OAB treatment, mirabegron addresses key limitations of traditional antimuscarinic therapies, such as cholinergic side effects, by offering a distinct mechanism focused on sympathetic modulation.^[12]

Pharmacokinetics

Mirabegron is rapidly absorbed after oral administration, with time to maximum plasma concentration (T_max) occurring approximately 3 to 5 hours post-dose.^[13]^[3] The absolute oral bioavailability ranges from 29% at a 25 mg dose to 35% at a 50 mg dose, with exposure increasing in a greater-than-proportional manner at higher doses.^[14]^[3] In adults, food has no clinically significant effect on bioavailability or overall exposure (AUC), though a high-fat meal may slightly reduce C_max by about 40% and delay T_max by 1 to 2 hours without necessitating dose adjustments.^[13]^[15] Following absorption, mirabegron is widely distributed throughout the body, with an apparent steady-state volume of distribution of approximately 1670 L after intravenous administration, indicating extensive tissue distribution.^[13]^[14] It is highly bound to plasma proteins, approximately 71%, primarily to albumin and alpha-1-acid glycoprotein.^[3]^[14] Mirabegron undergoes extensive hepatic metabolism to pharmacologically inactive metabolites via multiple pathways, including N-dealkylation, hydroxylation, direct glucuronidation, and amide hydrolysis; the cytochrome P450 enzymes CYP3A4 and CYP2D6 play a role in oxidative metabolism, though their contribution is limited compared to non-CYP pathways such as butyrylcholinesterase-mediated hydrolysis and uridine 5'-diphospho-glucuronosyltransferase (UGT) enzymes.^[13]^[3] Unchanged mirabegron accounts for the majority of circulating drug, with metabolites being minor components in plasma.^[14] The terminal elimination half-life of mirabegron is approximately 50 hours in adults, supporting once-daily dosing.^[13]^[3] Elimination occurs primarily through renal and biliary routes, with about 55% of the administered dose recovered in urine and 35% in feces over several days, including both unchanged drug (around 25% in urine) and metabolites.^[14]^[3] Total plasma clearance is approximately 57 L/h following intravenous dosing, with renal clearance around 13 L/h; clearance is reduced in patients with moderate to severe renal impairment or hepatic impairment, leading to increased exposure.^[13]^[14] In pediatric patients aged 3 years and older weighing at least 35 kg, mirabegron pharmacokinetics differ from adults. Median T_max is 4-5 hours after a single dose and 3-4 hours at steady state under fed conditions. The area under the curve (AUC) increases by 120% in the fasted state compared to fed state, indicating a food effect that supports administration with food. The apparent volume of distribution (Vz/F) ranges from 4,895 to 13,726 L and increases with body weight. The terminal half-life is shorter, approximately 26-31 hours, and clearance increases with body weight.^[2]

Adverse effects

Common adverse effects

Mirabegron treatment is generally well tolerated in patients with overactive bladder, with common adverse effects primarily mild to moderate in severity. In pooled data from placebo-controlled clinical trials, the most frequently reported adverse effects occurring in more than 2% of patients included hypertension (7.5% for 50 mg and 11.3% for 25 mg, compared to 7.6% placebo), nasopharyngitis (3.5% for 25 mg and 3.9% for 50 mg, compared to 2.5% placebo), urinary tract infection (2.9% for 50 mg and 4.2% for 25 mg, compared to 1.8% placebo), and headache (2.1% for 25 mg and 3.2% for 50 mg, compared to 3.0% placebo).^[4] Other common adverse effects (1% to 10% incidence) encompass constipation (up to 4.2% in combination therapy), tachycardia (0.9% to 2.2%), and nausea (less than 2%). Mirabegron is associated with small, dose-related increases in heart rate, with mean changes of 1 to 2 beats per minute observed in clinical trials. Similarly, mean increases in systolic blood pressure of 3 to 4 mmHg have been noted, though these are typically reversible upon discontinuation.^[4]^[3] In phase III clinical trials, the incidence of treatment discontinuation due to adverse effects ranged from 5.9% to 6.4% for mirabegron, comparable to rates observed with placebo. Due to the potential for blood pressure elevation, regular monitoring of blood pressure is recommended, particularly in patients with hypertension.^[4]^[16]^[3]

Pediatric use

In pediatric patients aged 3 years and older with neurogenic detrusor overactivity (weighing at least 35 kg), common adverse effects (≥3% incidence) from clinical trials include urinary tract infection (24.4%), nasopharyngitis (5.8%), constipation (4.7%), and headache (3.5%).^[5]

Serious adverse effects

Mirabegron, a beta-3 adrenergic agonist used for overactive bladder, is associated with several rare but serious adverse effects, occurring in less than 1% of patients in clinical trials. Urinary retention has been reported, particularly in individuals with bladder outlet obstruction or those concurrently using antimuscarinic medications, potentially leading to acute complications requiring intervention. Angioedema, involving swelling of the face, lips, tongue, or larynx, has also been documented and can be life-threatening if it affects the upper airway, necessitating immediate discontinuation of the drug and appropriate medical management.^[3] Cardiovascular risks include tachycardia and hypersensitivity reactions, which may manifest as severe allergic responses. Post-marketing surveillance has identified reports of severe hypertension and arrhythmias, such as atrial fibrillation, underscoring the need for caution in patients with pre-existing cardiac conditions, although no black box warning has been issued.^[3] Additionally, mirabegron may cause QT prolongation at supratherapeutic doses, with mean increases of up to 8.1 msec observed at 200 mg, though effects at therapeutic doses (50 mg) are minimal (3.7 msec); it is generally avoided in patients with severe uncontrolled hypertension (systolic ≥180 mmHg or diastolic ≥110 mmHg). In long-term clinical trials extending up to 12 months, no increased risk of malignancy was observed with mirabegron use, consistent with nonclinical carcinogenicity studies in rats and mice showing no evidence of tumor development at exposures up to 45-fold the maximum recommended human dose. While mild tachycardia is a more common effect, especially in combination therapy, monitoring for escalation to serious arrhythmias is advised in at-risk populations.^[3]

Interactions

Drug interactions

Mirabegron undergoes metabolism primarily via cytochrome P450 (CYP) enzymes, including CYP3A4 and CYP2D6, which can lead to pharmacokinetic interactions with drugs that inhibit or induce these enzymes or are substrates for them.^[4] As a moderate inhibitor of CYP2D6, mirabegron can increase systemic exposure to CYP2D6 substrates, potentially enhancing their effects or toxicity. For example, co-administration with metoprolol results in a 90% increase in C_max and 229% increase in AUC, while desipramine exposure rises with a 79% increase in C_max and 241% increase in AUC.^[4] Monitoring for adverse effects and dose adjustments are recommended, particularly for narrow therapeutic index CYP2D6 substrates such as thioridazine, flecainide, or propafenone.^[4] Exposure to mirabegron may be higher (AUC increased by up to 31%) in CYP2D6 poor metabolizers, but no dose adjustment is required.^[9] CYP3A4 inhibitors and inducers also affect mirabegron exposure due to its partial metabolism by this enzyme. Strong CYP3A4 inhibitors like ketoconazole increase mirabegron C_max by 45% and AUC by 80%.^[4] Conversely, strong CYP3A4 inducers such as rifampin decrease mirabegron AUC by approximately 66% and C_max by 62%, potentially reducing its efficacy.^[4] In patients with mild or moderate renal or hepatic impairment, the mirabegron dose should be limited to 25 mg daily when co-administered with strong CYP3A4 inhibitors, and use is not recommended in severe renal impairment or moderate hepatic impairment with such inhibitors.^[17] Mirabegron, as a weak inhibitor of P-glycoprotein (P-gp), can elevate digoxin levels. Co-administration increases digoxin C_max by 29% and AUC by 27%.^[4] The lowest effective dose of digoxin should be prescribed, with serum concentrations monitored and titrated accordingly.^[4] When combined with antimuscarinics such as solifenacin, no clinically significant pharmacokinetic interactions occur, and fixed-dose combinations are approved for overactive bladder treatment.^[17] However, additive effects may increase the risk of urinary retention, necessitating caution and monitoring in patients receiving both agents.^[4] No new clinically significant drug interactions have been identified in postmarketing surveillance as of 2025.^[18]

Other interactions

Mirabegron exhibits no clinically significant pharmacokinetic changes when administered with food in adults, though a high-fat meal reduces the area under the curve (AUC) by approximately 17% and peak plasma concentration (C_max) by 45%. A low-fat meal results in greater reductions (AUC by 51%, C_max by 75%). The drug may be taken with or without food, but patients should maintain consistent administration relative to meals to ensure steady exposure levels.^[4] No direct pharmacokinetic interaction occurs between mirabegron and alcohol, and the dissolution rate of mirabegron granules may increase in the presence of alcohol in vitro, though the clinical impact remains unevaluated. However, alcohol consumption can exacerbate overactive bladder symptoms such as urgency, frequency, and incontinence, and may contribute to dehydration, potentially worsening urinary issues.^[19]^[20]

History

Development

Mirabegron was discovered and developed by Astellas Pharma Inc. as the first selective β3-adrenoceptor agonist specifically targeted for the treatment of overactive bladder (OAB), emerging as a novel alternative to antimuscarinic agents, which are associated with cognitive side effects such as dry mouth and constipation.^[21] The compound, chemically known as 2-(2-aminothiazol-4-yl)-N-[4-(2-[(2R)-2-hydroxy-2-phenylethyl]amino)ethyl)phenyl]acetamide, was synthesized in the late 1990s following research into β3-adrenoceptors dating back to 1989, with preclinical optimization occurring through the early 2000s. Preclinical studies demonstrated mirabegron's efficacy in animal models of bladder dysfunction, including rats and monkeys, where it increased bladder capacity and reduced detrusor overactivity during the storage phase without impairing voiding contractions.^[21] In rat models of bladder outlet obstruction, mirabegron dose-dependently decreased non-voiding contractions, confirming its selectivity for β3-adrenoceptors (EC50 of 0.016 µM in vitro) and potential to address storage symptoms in OAB.^[21] These findings positioned mirabegron as the inaugural compound in its class to exhibit robust preclinical efficacy across multiple models of storage bladder dysfunction.^[21] The core invention was protected under US Patent No. 6,346,532, granted in 2002 to Yamanouchi Pharmaceutical Co., Ltd. (predecessor to Astellas), covering phenethylamine derivatives as β3-adrenoceptor agonists for therapeutic use. Clinical development of mirabegron spanned from 2002 to 2012 and encompassed 41 studies involving over 10,000 individuals, including 8,433 patients with OAB symptoms.^[22] The Phase I program, comprising 29 studies with 1,462 healthy volunteers, focused on pharmacokinetics, safety, and tolerability, establishing once-daily dosing feasibility.^[21] Phase II efforts included three dose-ranging and proof-of-concept trials (e.g., BLOSSOM and DRAGON) with 1,179 OAB patients, which supported advancement by showing reductions in urgency and incontinence episodes compared to placebo.^[21] Phase III trials, consisting of six multicenter, randomized, double-blind studies (e.g., SCORPIO, ARIES, CAPRICORN, and TAURUS), evaluated efficacy and long-term safety over 12 to 52 weeks.^[21] Key among these was the SCORPIO trial (178-CL-046; NCT00689104), a 12-week study in 1,978 patients that demonstrated mirabegron 50 mg and 100 mg doses significantly superior to placebo in reducing the mean number of micturitions per 24 hours by 1.93 (50 mg) and 1.77 (100 mg) versus 1.34 for placebo (both p < 0.001) and the mean number of urgency incontinence episodes per 24 hours by 1.57 (50 mg) and 1.46 (100 mg) versus 1.12 for placebo (both p < 0.05). The TAURUS trial (178-CL-049; NCT00688688), involving 2,444 patients over 52 weeks, further confirmed sustained efficacy in urgency reduction and overall tolerability.^[23] These results underscored mirabegron's role in improving OAB symptoms while minimizing antimuscarinic-related adverse effects.^[21]

Regulatory approvals

Mirabegron received its first regulatory approval in Japan on July 1, 2011, for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and frequent urination in adults, marketed as Betanis by Astellas Pharma.^[24] This marked the initial global authorization for the drug following its development as a selective β3-adrenoceptor agonist. Subsequently, the U.S. Food and Drug Administration (FDA) approved mirabegron on June 28, 2012, under the brand name Myrbetriq, for the treatment of OAB in adults, based on pivotal phase III trials demonstrating efficacy in reducing incontinence episodes and micturition frequency.^[25] In Europe, the European Medicines Agency (EMA) granted marketing authorization for mirabegron on December 20, 2012, as Betmiga for the symptomatic treatment of urgency, increased micturition, and/or urgency incontinence in adults with OAB, following positive opinion from the Committee for Medicinal Products for Human Use (CHMP).^[26] Health Canada issued a Notice of Compliance for Myrbetriq on March 6, 2013, approving it for the same adult OAB indications as in the U.S.^[27] Label expansions followed initial approvals. The FDA approved a supplemental new drug application in May 2018 for the use of mirabegron in combination with solifenacin succinate (VESIcare) to treat OAB symptoms in adults, supported by phase III data showing improved efficacy over monotherapy.^[28] In 2021, the FDA extended approval to pediatric patients aged 3 years and older with neurogenic detrusor overactivity (NDO), including an extended-release granule formulation, based on safety and pharmacokinetic studies in children. The EMA similarly extended authorization on August 22, 2024, for NDO in pediatric patients aged 3 to less than 18 years via a new granule formulation, fulfilling pediatric investigation plan requirements.^[29] Regarding generics, the FDA granted tentative approval for mirabegron extended-release tablets in 2022 to manufacturers including Lupin Limited, acknowledging bioequivalence but delaying market entry due to exclusivity periods.^[30] Full approval and launches occurred in 2024, with companies such as Zydus Lifesciences and Lupin introducing generic versions following patent expirations, enhancing accessibility for OAB treatment.^[31]

Society and culture

Brand names

Mirabegron is the international nonproprietary name (INN) assigned to the drug by the World Health Organization.^[26] The systematic chemical name is 2-(2-aminothiazol-4-yl)-N-[4-(2-[(2R)-2-hydroxy-2-phenylethyl]amino)ethyl)phenyl]acetamide.^[32] It is pronounced /ˌmɪrəˈbɛɡrɒn/.^[33] In the United States, mirabegron is marketed under the brand name Myrbetriq by Astellas Pharma.^[34] In the European Union, it is available as Betmiga, also developed by Astellas.^[26] In Japan, the brand name is Betanis, approved and distributed by Astellas.^[35] Other international brand names include Incrabloc in India and Mirago in various markets such as India.^[36]^[37] These names reflect regional marketing strategies by manufacturers and licensees, with availability varying by country.^[14]

Availability and generics

Mirabegron is available by prescription only in most countries worldwide, reflecting its status as a prescription-only medication for overactive bladder treatment. In the United States, it was the 214th most commonly prescribed medication in 2023, with approximately 2 million prescriptions dispensed.^[38] Generic versions of mirabegron have entered the market following key regulatory milestones. In the United States, the Food and Drug Administration approved abbreviated new drug applications (ANDAs) for generic mirabegron extended-release tablets as early as September 2022, with companies such as Lupin Limited and Zydus Lifesciences receiving approvals; these launches occurred "at risk" amid ongoing patent litigation, as the pediatric exclusivity expired in September 2024, enabling broader generic competition despite some formulation patents extending to 2030. Generic versions launched in the US in 2024 by companies including Lupin and Zydus, following court decisions in ongoing patent litigation.^[39]^[40]^[41]^[42] In the European Union, generic mirabegron prolonged-release tablets gained marketing authorization through decentralized procedures, with approvals anticipated and achieved around mid-2024 by manufacturers like Adalvo, building on the original Betmiga authorization from 2012.^[43]^[26] The availability of generics has substantially lowered costs, making treatment more accessible. Branded mirabegron (such as Myrbetriq) typically costs around $380–$450 for a 30-day supply of 50 mg tablets in the US without insurance, while generic equivalents are priced at approximately $50–$100 for the same quantity, depending on the pharmacy and discounts.^[44]^[45] Mirabegron is widely accessible in North America, Europe, and parts of Asia, where overactive bladder treatment markets are well-established and reimbursement policies support uptake. However, its availability remains limited in low- and middle-income countries due to high out-of-pocket costs and less developed healthcare infrastructure, though approvals in 67 nations globally (as of June 2024) indicate gradual expansion.^[46]^[47]^[48]

Research

Overactive bladder advancements

Recent clinical trials from 2024 and 2025 have highlighted mirabegron's advantages in managing overactive bladder (OAB) symptoms compared to other agents. In a multicenter study conducted in Latin American patients, mirabegron demonstrated superior efficacy over darifenacin in reducing both daytime and nighttime micturition frequency, with decreases of 2.87 and 1.25 urinations per day, respectively, versus non-significant changes with darifenacin.^[49] This superiority was attributed to mirabegron's better tolerability profile, including lower rates of adverse events (3.2% vs. 12.8%) and discontinuation (3.8% vs. 12.8%). Additionally, combination therapy with mirabegron and tamsulosin showed enhanced outcomes in men with OAB and benign prostatic hyperplasia (BPH), achieving a greater reduction in International Prostate Symptom Score (IPSS) of -10.85 compared to -9.85 with tamsulosin monotherapy alone, alongside improvements in urgency, incontinence, and quality of life measures.^[50]^[51] Studies on dosing timing have further refined mirabegron's application in OAB treatment. A randomized controlled trial presented at the International Continence Society (ICS) 2024 meeting evaluated daytime versus nighttime administration of mirabegron 25 mg in women with OAB syndrome over 12 weeks. Both regimens led to significant improvements in Overactive Bladder Symptom Score (OABSS), with no overall between-group differences in efficacy; however, nighttime dosing provided greater short-term benefits for nocturia and morning urgency, while daytime dosing better addressed daytime urgency and emotional well-being.^[52] Emerging research on treatment discontinuation supports strategies for stable OAB patients. A 2025 prospective randomized trial protocol investigated withdrawal approaches for mirabegron in children with urinary incontinence who achieved continence after at least 3 months of therapy, comparing abrupt cessation to gradual tapering over 14 days, with monitoring for recurrence up to 12 months post-withdrawal.^[53] Meta-analyses underscore mirabegron's favorable profile relative to alternatives in OAB care.^[54]

Emerging indications

Mirabegron, a β3-adrenergic receptor agonist, has shown potential in investigational applications beyond its established uses, particularly in metabolic and antimicrobial contexts. In a 2023 preclinical study using diet-induced obese mice, the combination of mirabegron and metformin resulted in an additive 17% body weight loss, surpassing the effects of either drug alone by 6-13%, suggesting synergistic mechanisms in obesity management.^[55] A 2020 human clinical trial involving chronic mirabegron administration (50 mg/day for 12 weeks) in obese, insulin-resistant men demonstrated improved insulin sensitivity and glucose effectiveness without significant weight reduction, highlighting its role in enhancing metabolic parameters.^[56] Ongoing research into mirabegron's activation of brown adipose tissue (BAT) continues to explore its thermogenic effects, with studies indicating increased BAT activity and potential for broader metabolic benefits in humans.^[57] Emerging evidence also points to mirabegron's antibacterial properties. A 2025 in vitro study revealed that mirabegron inhibits Escherichia coli growth and modulates immune responses in urinary tract models, proposing its utility in preventing urinary tract infections (UTIs) through direct antimicrobial and immunomodulatory actions.^[58] In combination therapies, a 2025 randomized controlled trial evaluated mirabegron (50 mg/day) alongside acupuncture for overactive bladder (OAB) symptoms, including nocturia; the combination significantly improved Overactive Bladder Symptom Scores (OABSS) and demonstrated sustained efficacy at 12 weeks compared to mirabegron monotherapy, with no increase in adverse events.^[59] Regarding cognitive health, a 2025 Danish nationwide active comparator cohort study published in BMJ Medicine found that anticholinergic bladder drugs were associated with increased dementia risk compared to non-use (IRR 1.44, 95% CI 1.40-1.48), with risk varying by cumulative dose; however, when compared to mirabegron, anticholinergics showed no increased risk (IRR 0.82, 95% CI 0.74-0.92).^[60] Pediatric applications are under investigation, with a 2025 prospective study assessing mirabegron (starting at 25 mg/day) in children aged 5-15 years with non-neurogenic OAB; it showed superior efficacy to solifenacin, with 94.4% achieving ≥50% reduction in Dysfunctional Voiding Symptom Score (DVSS) compared to 75% (p=0.02), significant reductions in incontinence episodes (p<0.001) and urgency, and a favorable safety profile with fewer adverse effects (19.4% vs. 47.2%, p=0.01), including minimal gastrointestinal side effects.^[61]