Mirabegron

What it is

Mirabegron is a synthetic small molecule taken by mouth as a 25 mg or 50 mg extended-release tablet, and as granules made up into an extended-release oral suspension for children. It is the first beta-3 adrenergic receptor agonist licensed for overactive bladder, and it works by a different route from the older antimuscarinic bladder drugs. It is handled by several pathways at once: it is a substrate for CYP3A4, CYP2D6, butyrylcholinesterase, UGT, P-glycoprotein and the organic cation transporters, and it is itself a moderate inhibitor of CYP2D6.

What the research says

In three 12-week placebo-controlled trials the absolute effect is small and measurable: about 0.3 to 0.4 fewer wetting episodes and about 0.4 to 0.6 fewer trips to the toilet per 24 hours than placebo, on a baseline of roughly 2.5 to 3 episodes and about 11.5 micturitions a day. A network meta-analysis of 64 trials found it significantly better than placebo on every efficacy endpoint and broadly similar to common antimuscarinics, with clearly less dry mouth, constipation and urinary retention. Its distinctive harms are a rise in blood pressure, hypertension reported as an adverse reaction, angioedema, and urinary retention in people with bladder outlet obstruction or taking an antimuscarinic as well. It has no boxed warning.

Evidence grade: Well established.

How it works

Drug class: Beta-3 adrenergic receptor agonist (beta-3 agonist) for overactive bladder; also a moderate CYP2D6 inhibitor

The bladder muscle carries beta-3 adrenergic receptors. Mirabegron switches these on, which relaxes the bladder muscle during the filling part of the cycle so the bladder holds more before it signals the urge to go. That is the opposite approach to the older antimuscarinic drugs, which block a different receptor; it is why mirabegron causes much less dry mouth. At high doses it starts to stimulate beta-1 receptors too, which is the likely route to its effects on heart rate and blood pressure. (Source 1)

What it is used for

• Three 12-week placebo-controlled trials met both co-primary endpoints, with small absolute reductions in wetting episodes and in daily voids. A 64-study network meta-analysis places it roughly level with common antimuscarinics for efficacy and clearly ahead on anticholinergic tolerability. Evidence: established. (Source 2)
• Approved as combination therapy. The network meta-analysis found solifenacin 5 mg plus mirabegron more efficacious than mirabegron alone on some or all outcomes, at the cost of the antimuscarinic side effects. Evidence: established. (Source 3)
• Approved, with a separate granule formulation. The label's own warnings note blood-pressure rises may be larger in children aged 3 to under 12 than in adolescents, and the paediatric pharmacokinetics are strongly food-dependent. Evidence: limited. (Source 4)
• Off-label. A network meta-analysis of 16 studies and 2,002 patients found mirabegron, solifenacin and tamsulosin all better than placebo for urinary symptoms, with mirabegron ranked best for body pain, sexual matters and adverse events. The authors say better randomised trials are still needed. Evidence: limited. (Source 5)
• Off-label add-on. A Bayesian network meta-analysis of 18 trials found mirabegron reduced micturitions by 0.46 per 24 hours versus control, a credible interval that only just excludes no effect, and found no established advantage either way between vibegron and mirabegron. Evidence: limited. (Source 6)

Interactions

• Any drug cleared by CYP2D6, as a class (label): Mirabegron is itself a moderate inhibitor of CYP2D6, so anything that enzyme normally clears builds up. The label asks for monitoring and possible dose adjustment, especially for drugs with a narrow margin between a useful and a toxic level. (Source 7)
• Metoprolol (pharmacokinetic study): Mirabegron blocks CYP2D6, the enzyme that clears metoprolol, so metoprolol levels rise sharply. In a healthy-volunteer study metoprolol exposure more than tripled. (Source 8)
• Desipramine and other narrow-therapeutic-index CYP2D6 substrates (pharmacokinetic study): Desipramine exposure rose about three-and-a-half-fold when given with mirabegron. The label asks for monitoring and possible dose reduction of any CYP2D6 substrate with a narrow margin of safety. (Source 8)
• Digoxin (pharmacokinetic study): Mirabegron raised digoxin peak levels by 29% and exposure by 27%. The label asks for the lowest digoxin dose at the start and for digoxin levels to guide titration. (Source 9)
• Warfarin (pharmacokinetic study): A single-dose study showed only a 4% to 9% change in warfarin levels and no effect on INR or prothrombin time, but the effect of mirabegron on repeated warfarin dosing has not been fully studied. (Source 10)
• Alcohol (pharmacokinetic study): Adding alcohol speeds up how fast mirabegron comes out of the granule formulation at near-neutral pH, and the clinical consequence has not been studied. The extended-release tablet is not affected at any pH. (Source 11)
• Food (pharmacokinetic study): For adults the tablet can be taken with or without food. For children the picture is the opposite: taking the granules or tablet on an empty stomach raises exposure substantially, which is why the paediatric instruction is to take it with food. (Source 12)
• Herbal medicines (case reports): The label records one case of Stevens-Johnson syndrome with raised liver enzymes and bilirubin in a patient taking mirabegron 100 mg together with a herbal product. This is a single report and does not establish which agent was responsible. No study of mirabegron with St John's wort, grapefruit juice or any named supplement appears on the label read here. (Source 13)
• Sulfonylurea diabetes drugs, and drugs cleared by CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19 or CYP2E1 (theoretical): These are the interactions laboratory work predicts will not matter: mirabegron did not inhibit those enzymes at clinically relevant concentrations and did not affect glibenclamide or tolbutamide metabolism. (Source 11)

Stopping it

• No withdrawal syndrome, rebound or taper appears on the label read here. The only stopping instruction is immediate discontinuation if angioedema involves the tongue, hypopharynx or larynx. (Source 14)
• A missed dose is simply taken late or skipped; there is no tapering schedule. (Source 15)
• In practice most people stop early of their own accord. In a national database of nearly two million people the median time on mirabegron was 56 days, and the median proportion of days covered was 0.18, meaning people took it on under a fifth of the days they could have. (Source 16)
• Head-to-head data put mirabegron behind vibegron on staying on treatment, with a higher continuation rate and a lower discontinuation rate for vibegron. (Source 17)

What goes wrong

Hypertension was the most commonly reported adverse reaction, but the pattern across doses is not a simple dose response: it exceeded placebo at 25 mg and not at 50 mg. (Source 18)

• Randomized trial, Moderate certainty.
• Size: 1380 placebo, 432 mirabegron 25 mg, 1375 mirabegron 50 mg across Studies 1, 2 and 3.
• Who: Adults with overactive bladder.
• How long: Up to 12 weeks.
• Result: Hypertension (including blood pressure above the normal range or increased from baseline) 7.6% on placebo, 11.3% at 25 mg and 7.5% at 50 mg; tachycardia 0.6%, 1.6% and 1.2%; urinary tract infection 1.8%, 4.2% and 2.9%.
• Funding: industry-funded (sponsor's label)

Limit of this finding: The asterisk after Hypertension is DailyMed's own footnote marker, and the footnote it points to is carried at the foot of the same block: the entry counts reports of blood pressure above the normal range and blood pressure increased from baseline, occurring predominantly in subjects who already had high blood pressure. So the 7.6, 11.3 and 7.5 are not all newly diagnosed hypertension. The dose pattern is also not a simple one: the figure is higher at 25 mg than at 50 mg, and only 432 patients took 25 mg against 1375 at 50 mg, so the 25 mg figure rests on far fewer people.

Number of Patients 1380 432 1375 Hypertension* 7.6 11.3 7.5 Nasopharyngitis 2.5 3.5 3.9 Urinary Tract Infection 1.8 4.2 2.9

In healthy volunteers mirabegron 50 mg raised supine blood pressure by about 3.5/1.5 mm Hg above placebo, while in patients with overactive bladder the rise was about 0.5 to 1 mm Hg. (Source 4)

• Randomized trial, Moderate certainty.
• Size: Two randomised placebo-controlled healthy-volunteer studies plus the patient trials.
• Who: Healthy adult volunteers, and adults with overactive bladder.
• How long: Not stated.
• Result: Mean maximum increase in systolic/diastolic blood pressure approximately 3.5/1.5 mm Hg greater than placebo at 50 mg in volunteers; approximately 0.5 to 1 mm Hg greater than placebo in patients. Not recommended in severe uncontrolled hypertension, defined as systolic 180 mm Hg or more and/or diastolic 110 mm Hg or more.
• Funding: industry-funded (sponsor's label)

In two, randomized, placebo-controlled, healthy adult volunteer studies, MYRBETRIQ was associated with dose-related increases in supine blood pressure. In these studies, at the maximum recommended dose of 50 mg, the mean maximum increase in systolic/diastolic blood pressure was approximately 3.5/1.5 mm Hg greater than placebo. In contrast, in adult OAB patients in clinical trials, MYRBETRIQ, taken as monotherapy or in combination with solifenacin succinate 5 mg, the mean increase in systolic and diastolic blood pressure at the maximum recommended mirabegron dose of 50 mg was approximately 0.5 to 1 mm Hg greater than placebo. Worsening of pre-existing hypertension was reported infrequently in patients taking MYRBETRIQ.

Urinary retention has been reported in people with bladder outlet obstruction and in people also taking an antimuscarinic for overactive bladder, although a controlled safety study in obstruction did not show an increase. (Source 19)

• Randomized trial, Low certainty.
• Size: A controlled clinical safety study in patients with bladder outlet obstruction; size not given on the label.
• Who: Patients with bladder outlet obstruction, and patients on muscarinic antagonists.
• How long: Not stated.
• Result: No increased urinary retention demonstrated in the controlled study; postmarketing reports nonetheless led to a caution and a monitoring instruction.
• Funding: industry-funded (sponsor's label)

Limit of this finding: No source read for this entry gives a rate for urinary retention with mirabegron. The label records that it has been reported in people with bladder outlet obstruction and in people also taking an antimuscarinic, and that the controlled safety study in obstruction did not show an increase, but it gives no number and no denominator for either statement. That absence is stated here rather than filled in with a figure from elsewhere.

In patients taking MYRBETRIQ, urinary retention has been reported to occur in patients with bladder outlet obstruction (BOO) and in patients taking muscarinic antagonist medications for the treatment of OAB. A controlled clinical safety study in patients with BOO did not demonstrate increased urinary retention in patients treated with mirabegron; however, MYRBETRIQ should still be administered with caution to patients with clinically significant BOO. For example, monitor these patients for signs and symptoms of urinary retention.

Angioedema of the face, lips, tongue or larynx has been reported, sometimes after the first dose, and may be life-threatening. (Source 14)

• Case series, Very low certainty.
• Size: Postmarketing reports; no count given.
• Who: People taking mirabegron tablets or granules.
• How long: Hours after the first dose, or after multiple doses.
• Result: No rate given on the label.
• Funding: industry-funded (sponsor's label)

Angioedema of the face, lips, tongue, and/or larynx has been reported with MYRBETRIQ/MYRBETRIQ Granules. In some cases, angioedema occurred after the first dose, however, cases have been reported to occur hours after the first dose or after multiple doses. Angioedema, associated with upper airway swelling, may be life-threatening.

In the 52-week active-controlled study, discontinuations for constipation, headache and hypertension were under 1%, and two patients had transaminases rise more than tenfold. (Source 20)

• Randomized trial, Moderate certainty.
• Size: 812 patients on mirabegron 50 mg and 812 on active control in Study 4.
• Who: Adults with overactive bladder.
• How long: Up to 52 weeks.
• Result: Discontinuations: constipation 0.9%, headache 0.6%, dizziness 0.5%, hypertension 0.5%; serious adverse events exceeding active control: cerebrovascular accident 0.4%, osteoarthritis 0.2%; ALT/AST rose more than 10-fold in 2 patients (0.3%) and returned to baseline on continued treatment.
• Funding: industry-funded (sponsor's label)

In Study 4, in patients treated with MYRBETRIQ 50 mg once daily, adverse reactions leading to discontinuation reported by more than 2 patients and at a rate greater than active control included: constipation (0.9%), headache (0.6%), dizziness (0.5%), hypertension (0.5%), dry eyes (0.4%), nausea (0.4%), vision blurred (0.4%), and urinary tract infection (0.4%). Serious adverse events reported by at least 2 patients and exceeding active control included cerebrovascular accident (0.4%) and osteoarthritis (0.2%). Serum ALT/AST increased from baseline by greater than 10-fold in 2 patients (0.3%) taking MYRBETRIQ 50 mg; and these markers subsequently returned to baseline while both patients continued MYRBETRIQ.

Serious adverse events of neoplasm were reported more often at 100 mg than at 50 mg or on active control in the 52-week study, with no causal relationship established. (Source 13)

• Randomized trial, Low certainty.
• Size: Study 4: 812 on 50 mg, 820 on 100 mg, 812 on active control.
• Who: Adults with overactive bladder.
• How long: Up to 52 weeks.
• Result: Neoplasm serious adverse events 0.1% at 50 mg, 1.3% at 100 mg and 0.5% on active control; breast cancer, malignant lung neoplasm and prostate cancer each in 2 patients at 100 mg.
• Funding: industry-funded (sponsor's label)

In Study 4, serious adverse events of neoplasm were reported by 0.1%, 1.3%, and 0.5% of patients treated with MYRBETRIQ 50 mg, MYRBETRIQ 100 mg, and active control once daily, respectively. Neoplasms reported by 2 patients treated with MYRBETRIQ 100 mg included breast cancer, lung neoplasm malignant, and prostate cancer. A causal relationship between mirabegron and these reported neoplasms has not been established.

In healthy volunteers, single doses up to 400 mg and multiple doses up to 300 mg daily raised pulse rate and systolic blood pressure. (Source 21)

• Randomized trial, Low certainty.
• Size: 6 subjects at the 400 mg single dose.
• Who: Healthy volunteers.
• How long: Single dose, and 10 days of multiple dosing.
• Result: At 400 mg, palpitations in 1 of 6 subjects and pulse rate above 100 bpm in 3 of 6; multiple doses up to 300 mg daily for 10 days increased pulse rate and systolic blood pressure.
• Funding: industry-funded (sponsor's label)

Mirabegron has been administered to healthy volunteers at single doses up to 400 mg. At this dose, adverse events reported included palpitations (1 of 6 subjects) and increased pulse rate exceeding 100 beats per minute (bpm) (3 of 6 subjects). Multiple doses of mirabegron up to 300 mg daily for 10 days showed increases in pulse rate and systolic blood pressure when administered to healthy volunteers.

The label warns that blood pressure increases may be larger in children aged 3 to under 12 than in adolescents, and sets the paediatric not-recommended threshold by percentile rather than by a fixed figure. (Source 22)

• Official position, Certainty not rated.
• Size: Not applicable.
• Who: Children aged 3 years to under 18 years with neurogenic detrusor overactivity.
• How long: Not stated; periodic blood pressure determinations are recommended.
• Result: Not recommended in paediatric patients with severe uncontrolled hypertension, defined as a systolic and/or diastolic blood pressure above the 99th percentile plus 5 mm Hg for age, sex and stature.
• Funding: industry-funded (sponsor's label)

Limit of this finding: The paediatric threshold is not a single number: it depends on the child's age, sex and height, so it cannot be read off the way the adult 180/110 mm Hg figure can. No effect size is given for how much blood pressure rises in children, only that the increase may be larger in the younger group.

Blood pressure increases may be larger in children (3 to less than 12 years of age) than in adolescents (12 to less than 18 years of age).

What the evidence supports

Across three 12-week placebo-controlled trials, mirabegron 50 mg reduced incontinence episodes by about 0.34 to 0.42 per 24 hours more than placebo. (Source 2)

• Randomized trial, Moderate certainty.
• Size: Incontinence analysis restricted to patients with at least 1 episode at baseline: Study 1 n=291 placebo / 293 mirabegron 50 mg; Study 2 n=325 / 312; Study 3 n=262 placebo / 254 at 25 mg / 257 at 50 mg.
• Who: Adults with overactive bladder, 94% Caucasian, 72% female, mean age 59 years (range 18-95), about half with prior antimuscarinic treatment.
• How long: 12 weeks.
• Result: Baseline about 2.43 to 3.03 episodes per 24 h. Difference from placebo (adjusted mean) -0.41 (95% CI -0.72, -0.09) in Study 1; -0.34 (-0.66, -0.03) in Study 2; -0.40 (-0.74, -0.06) at 25 mg and -0.42 (-0.76, -0.08) at 50 mg in Study 3.
• Funding: industry-funded (sponsor's registration programme reported in the label)

Difference from placebo (adjusted mean‡) -- -0.41 -- -0.34 -- -0.40 -0.42 95% Confidence Interval -- (-0.72, -0.09) -- (-0.66, -0.03) -- (-0.74, -0.06) (-0.76, -0.08)

On the second co-primary endpoint, mirabegron reduced the number of times people passed urine by about 0.42 to 0.61 per 24 hours more than placebo. (Source 23)

• Randomized trial, Moderate certainty.
• Size: Study 1 n=480 placebo / 473 mirabegron; Study 2 n=433 / 425; Study 3 n=415 placebo / 410 at 25 mg / 426 at 50 mg.
• Who: Same three trials.
• How long: 12 weeks.
• Result: Baseline about 11.5 to 11.8 micturitions per 24 h. Difference from placebo -0.60 (95% CI -0.90, -0.29), -0.61 (-0.98, -0.24), -0.47 (-0.82, -0.13) and -0.42 (-0.76, -0.08); p < 0.001, 0.001, 0.007 and 0.015.
• Funding: industry-funded (sponsor's registration programme reported in the label)

Number of Micturitions per 24 Hours n 480 473 433 425 415 410 426 Baseline (mean) 11.71 11.65 11.51 11.80 11.48 11.68 11.66

The review's own conclusion is that mirabegron 50 mg relieves key symptoms better than placebo and similarly to a range of common antimuscarinics with fewer anticholinergic side effects, and that adding solifenacin appears to provide an efficacy benefit. (Source 24)

• Systematic review, Moderate certainty.
• Size: Same 64 studies.
• Who: Adults with overactive bladder.
• How long: Not stated.
• Result: Authors' conclusion, not a numeric estimate. The journal's lay Patient Summary, printed immediately after it in the same record, puts the combination result more strongly, as 'more effective than mirabegron 50mg alone'.
• Funding: not stated in the abstract. This run reached only abstracts, so the paper's own funding and conflict-of-interest statement was not read; three of the named authors appear to be affiliated with the manufacturer, which is recorded here as unverified rather than asserted.

Limit of this finding: Two versions of the same result sit side by side in this record. The authors' CONCLUSIONS say the combination 'appears to provide an efficacy benefit'; the journal's PATIENT SUMMARY, written for a lay audience, says it 'was more effective than mirabegron 50mg alone'. The scientific conclusion is the more cautious of the two and is the one quoted here.

CONCLUSIONS: The relief of key OAB symptoms produced by mirabegron 50mg is significantly better than placebo, and similar to a range of common antimuscarinics, with the benefit of significantly fewer bothersome anticholinergic side effects such as dry mouth. Combination treatment of solifenacin 5mg plus mirabegron 25 or 50mg appears to provide an efficacy benefit compared with mirabegron 50mg, with the expected side effects of individual antimuscarinics.

The approved adult indication is narrow and symptom-defined: overactive bladder with urge incontinence, urgency and frequency, alone or combined with solifenacin. (Source 3)

• Official position, Certainty not rated.
• Size: Not applicable.
• Who: Adults with overactive bladder.
• How long: Not applicable.
• Result: The regulator's position as of the SPL version effective 2024-08-01; it is a licence, not an effect estimate.
• Funding: industry-funded (sponsor's label)

MYRBETRIQ Combination Therapy with Solifenacin Succinate MYRBETRIQ, in combination with the muscarinic antagonist solifenacin succinate, is indicated for the treatment of OAB in adult patients with symptoms of urge urinary incontinence, urgency, and urinary frequency.

On the incontinence co-primary endpoint the label reports p-values of 0.003, 0.026, 0.005 and 0.001, and says significance was declared at the 0.05 level with a multiplicity adjustment. (Source 2)

• Randomized trial, Moderate certainty.
• Size: Study 1 n=291 placebo / 293 mirabegron 50 mg; Study 2 n=325 / 312; Study 3 n=262 placebo / 254 at 25 mg / 257 at 50 mg, restricted to patients with at least 1 incontinence episode at baseline.
• Who: Adults with overactive bladder in Studies 1, 2 and 3.
• How long: 12 weeks.
• Result: p = 0.003 (Study 1, 50 mg), 0.026 (Study 2, 50 mg), 0.005 (Study 3, 25 mg) and 0.001 (Study 3, 50 mg); the table's footnote says the marked value was statistically significantly superior to placebo at the 0.05 level with multiplicity adjustment.
• Funding: industry-funded (sponsor's registration programme reported in the label)

Limit of this finding: These p-values belong with the differences from placebo quoted elsewhere in this entry, which are small: about a third to four tenths of one wetting episode per 24 hours against a baseline of about two and a half to three. A p-value says the difference is unlikely to be chance; it says nothing about whether a third of an episode a day is worth having.

p-value -- 0.003§ -- 0.026§ -- 0.005§ 0.001§

What the evidence does not support

In the same table, the increase in volume voided per micturition was not statistically significant at the 25 mg dose in Study 3. (Source 23)

• Randomized trial, Moderate certainty.
• Size: Study 3 volume-voided analysis n=415 placebo / 410 at 25 mg / 426 at 50 mg.
• Who: Same three trials.
• How long: 12 weeks.
• Result: Difference from placebo in volume voided 4.6 mL at 25 mg (95% CI -1.6, 10.8; p = 0.15) versus 12.4 mL at 50 mg (6.3, 18.6; p < 0.001)
• Funding: industry-funded (sponsor's registration programme reported in the label)

Volume Voided (mL) per Micturition n 480 472 433 424 415 410 426 Baseline (mean) 156.7 161.1 157.5 156.3 164.0 165.2 159.3 Change from baseline (adjusted mean‡) 12.3 24.2 7.0 18.2 8.3 12.8 20.7 Difference from placebo (adjusted mean‡) -- 11.9 -- 11.1 -- 4.6 12.4 95% Confidence Interval -- (6.3, 17.4) -- (4.4, 17.9) -- (-1.6, 10.8) (6.3, 18.6) p-value -- < 0.001§ -- 0.001§ -- 0.15 < 0.001§

A pooled analysis of six mirabegron-versus-vibegron studies, randomised and non-randomised, found vibegron reduced urgency and urge incontinence episodes more than mirabegron. (Source 17)

• Meta-analysis, Low certainty.
• Size: 6 studies met inclusion criteria.
• Who: Patients with overactive bladder in head-to-head comparisons.
• How long: Not stated in the abstract.
• Result: Vibegron gave a greater reduction in daily urgency episodes (SMD = 0.37, P = .0006) and in urge incontinence episodes (SMD = 0.33, P = .006) than mirabegron; no significant differences in other efficacy parameters or overall safety; vibegron had a higher continuation rate and lower discontinuation rate.
• Funding: not stated.

Limit of this finding: The journal's own title calls these head-to-head trials, but the methods section shows that non-randomised studies were included as well, assessed with the Newcastle-Ottawa Scale, and only six studies were included in all. The pooled standardised mean differences are therefore not from randomised trials alone, and the paper reports p-values without confidence intervals, so the precision of the estimates cannot be judged. The authors' own closing sentence is that additional randomised trials are needed to confirm the findings.

Six studies met the inclusion criteria. Vibegron was associated with a greater reduction in daily urgency episodes (standardized mean difference [SMD] = 0.37, P = .0006) and urinary urge incontinence (UUI) episodes (SMD = 0.33, P = .006) compared to mirabegron. However, no significant differences were found in other efficacy parameters or overall safety profiles. Vibegron demonstrated better adherence, with a higher continuation rate and lower discontinuation rate.

In men with benign prostatic hyperplasia on an alpha-1 blocker, an indirect comparison found no established advantage of vibegron over mirabegron, with every credible interval crossing no effect. (Source 6)

• Systematic review, Low certainty.
• Size: 18 trials included, 16 contributing quantitative data.
• Who: Men with BPH and persistent storage or overactive bladder symptoms despite alpha-1 blocker treatment.
• How long: Not stated in the abstract.
• Result: Mirabegron reduced micturitions by 0.46 per 24 h (95% CrI -0.88 to -0.02). Vibegron versus mirabegron: -0.35 micturitions per 24 h (-1.05 to 0.26) and -0.52 urgency episodes per day (-1.33 to 0.35), all credible intervals including the null; adverse-event odds inconclusive (OR 1.50, 0.69 to 3.14). Confidence low for the indirect and safety estimates.
• Funding: not stated.

Limit of this finding: The paper's title and key name mirabegron, but mirabegron is the comparator here, not the subject: the positive result is for vibegron against control. The authors state in their own conclusion that no advantage over mirabegron was established, and that every credible interval for the vibegron-versus-mirabegron comparison includes no difference. Nothing here shows mirabegron to be worse than vibegron in these men. The spaced minus signs in the numbers are the journal's own typography.

For vibegron versus mirabegron, indirect estimates were - 0.35 micturitions per 24 h (- 1.05 to 0.26) and - 0.52 urgency episodes per day (- 1.33 to 0.35), with all 95% CrIs including the null value. Reported AE odds were also inconclusive versus mirabegron (OR 1.50, 0.69 to 3.14), and AE definitions varied. Confidence was moderate for vibegron versus control on micturitions and urgency and low for indirect and safety estimates.

The same study found no statistically significant difference between mirabegron and antimuscarinics in falls or fractures, and the authors explicitly warn against reading that as equivalence. (Source 16)

• Cohort study, Low certainty.
• Size: Same 1,954,544 patients.
• Who: Same.
• How long: Same.
• Result: Composite falls/fractures adjusted HR 1.05 (95% CI 0.91-1.20; p = 0.519); falls 1.33 (0.66-2.68; p = 0.431); fractures 1.04 (0.90-1.19; p = 0.623)
• Funding: not stated.

Mirabegron and antimuscarinics had no statistically significant difference in the risk of composite falls/fractures (aHR 1.05 [95% CI 0.91-1.20]; p = 0.519), falls (1.33 [0.66-2.68]; p = 0.431), and fractures (1.04 [0.90-1.19]; p = 0.623). CONCLUSIONS: Persistence and adherence were significantly greater with mirabegron than antimuscarinics in patients receiving OAB treatment in Taiwan. No statistically significant association was observed for the incidence of falls/fractures between treatment groups. However, given the wide 95% CIs, the findings should not be interpreted as equivalence.

Where the evidence is mixed

A network meta-analysis of 64 trials found mirabegron 50 mg better than placebo on all efficacy endpoints but only comparable to most antimuscarinics, with solifenacin 10 mg more efficacious on some or all outcomes. (Source 25)

• Systematic review, Moderate certainty.
• Size: 64 studies, n=46 666.
• Who: Adults with overactive bladder in randomised controlled trials published 2000-2017.
• How long: Trial durations varied; not stated in the abstract.
• Result: Mirabegron 50 mg better tolerated for dry mouth, constipation and urinary retention than 21/22, 9/20 and 7/10 active comparators respectively; solifenacin 10 mg monotherapy and solifenacin 5 mg plus mirabegron were more efficacious for some or all outcomes.
• Funding: not stated in the abstract. This run reached only abstracts, so the paper's own funding and conflict-of-interest statement was not read; three of the named authors appear to be affiliated with the manufacturer, which is recorded here as unverified rather than asserted.

A total of 64 studies (n=46 666) were included in the network meta-analysis. Mirabegron 50mg was significantly more efficacious than placebo for all efficacy endpoints. Comparable overall efficacy was observed for mirabegron 50mg versus most active treatments, but solifenacin 10mg monotherapy and solifenacin 5mg plus mirabegron 25 or 50mg in combination were more efficacious for some/all outcomes. Mirabegron 50mg was significantly better tolerated regarding dry mouth, constipation, and urinary retention than 21/22, 9/20, and 7/10 active comparators, respectively; similar overall tolerability was observed between mirabegron 50mg and all treatments (including placebo) for the remaining endpoints.

The review's own limitation statement flags heterogeneity and inconsistent endpoint definitions across the included trials. (Source 25)

• Systematic review, Moderate certainty.
• Size: Same 64 studies.
• Who: Same.
• How long: Same.
• Result: No numeric estimate; a stated limitation.
• Funding: not stated in the abstract. This run reached only abstracts, so the paper's own funding and conflict-of-interest statement was not read; three of the named authors appear to be affiliated with the manufacturer, which is recorded here as unverified rather than asserted.

Limitations of the study included between-trial variations in the definition of certain endpoints and heterogeneity of the available data (eg, number of studies and patients assessed) for comparator treatments across different endpoints.

In a 2,091-patient uncontrolled retrospective study of a generic prolonged-release mirabegron, 8.8% had a systolic rise of at least 10 mmHg at 3 months, and the authors read that as no clinically meaningful increase. (Source 26)

• Cohort study, Low certainty.
• Size: 2,091 patients from 95 medical institutions in Korea.
• Who: Korean adults with overactive bladder prescribed mirabegron 50 mg prolonged release for at least 3 months, July 2020 to July 2021.
• How long: 3 months.
• Result: Systolic rise of at least 10 mmHg in 8.8%, at least 15 mmHg in 3.7%, at least 20 mmHg in 2.3%; diastolic rise of at least 5 mmHg in 16.8% and at least 10 mmHg in 6.7%; overall adverse-event incidence 2.1%, mostly mild; mean medication coverage 73.6%.
• Funding: not stated in the abstract; PubMed records the publication type Research Support, Non-U.S. Gov't and the study is of a named branded generic, so a commercial interest cannot be ruled out and is recorded here as unverified rather than guessed.

Limit of this finding: This study had no comparison group. It followed people who were all given the drug and looked at them again after three months, so the words 'effective and well-tolerated' describe a before-and-after change in one group, not a benefit over placebo or over another treatment. The symptom improvement was measured only in the subgroup whose symptom scores happened to be available, not in everyone enrolled. The blood-pressure conclusion sits against the manufacturer's own label, which warns that the drug can raise blood pressure and is not recommended in severe uncontrolled hypertension.

MATERIALS AND METHODS: Patients with OAB who were prescribed Selebeta® PR once daily for at least 3 months between July 2020 and July 2021 from 95 medical institutions in Korea were included.

In a national database study of nearly two million people, mirabegron was stopped later than antimuscarinics but still after a median of only 56 days. (Source 16)

• Cohort study, Low certainty.
• Size: 1,954,544 patients eligible, median age 60 years.
• Who: Taiwanese adults aged 20 and over starting a new overactive bladder drug between 2012 and 2018.
• How long: One year before and after the index prescription.
• Result: Median time to discontinuation 56 days (IQR 19-168) with mirabegron versus 14 days (5-42) with antimuscarinics; risk of discontinuation adjusted HR 1.58 (95% CI 1.55-1.61, p < 0.001) for antimuscarinics; median proportion of days covered 0.18 versus 0.03 (p < 0.001)
• Funding: not stated in the abstract; the abstract names no funder and this run did not reach the paper's funding statement, so it is recorded as unverified rather than guessed.

Median (interquartile range [IQR]) TTD was longer with mirabegron (56 [19-168] days) than antimuscarinics (14 [5-42] days) (risk of discontinuation aHR 1.58 [95% CI 1.55-1.61]; p < 0.001). Median (IQR) PDC was significantly higher with mirabegron (0.18 [0.06-0.52]) than antimuscarinics (0.03 [0.01-0.12]

In off-label use for ureteral stent symptoms, mirabegron was better than placebo but ranked below solifenacin for urinary symptoms, with the authors calling for better trials. (Source 5)

• Systematic review, Low certainty.
• Size: 16 studies, 2,002 patients.
• Who: Adults with ureteral stent-related symptoms.
• How long: Not stated in the abstract.
• Result: All regimens significantly better than placebo for urinary symptoms; mirabegron ranked best by SUCRA for body pain (71.5%), sexual matters (76.4%) and adverse events (70.5%); solifenacin ranked best for urinary symptoms (73.1%), general health (81.0%) and work performance (85.1%)
• Funding: not stated.

Limit of this finding: The percentages in this finding are SUCRA values, which are ranking probabilities from a network meta-analysis: they say how likely each drug is to come out on top for that outcome, not what proportion of patients improved and not by how much. '71.5%' does not mean 71.5% of people got better. The authors call for high-quality double-blind randomised trials before their observations are relied on.

Sixteen studies involving 2,002 patients were included. All regimens (including mirabegron, solifenacin, and tamsulosin) were significantly better than placebo in urinary symptoms. Solifenacin was associated with more adverse drug events than mirabegron and tamsulosin. The SUCRA values showed that mirabegron was the best in the outcomes of body pain (71.5%), sexual matters (76.4%), and adverse events (70.5%). Solifenacin was the best in the outcomes of urinary symptoms (73.1%), general health (81.0%), and work performance (85.1%). Tamsulosin had the lowest rate of all outcomes. CONCLUSIONS: Compared with traditional drugs for relieving SRSs, mirabegron performs best in terms of alleviating body pain, sexual matters, and adverse events, with little difference in urinary symptoms and general health. Further high-quality prospective double-blinded randomized controlled trials (RCTs) are required to provide sufficient evidence supporting our observations.

The table's own footnotes define its terms: the incontinence rows exclude anyone with no episodes at baseline, the changes are least-squares means adjusted for baseline, sex and region, and significance carried a multiplicity adjustment. (Source 23)

• Randomized trial, Moderate certainty.
• Size: Same three trials.
• Who: Adults with overactive bladder.
• How long: 12 weeks, with Week 12 taken as the last observation on treatment.
• Result: Volume voided rose 11.9, 11.1, 4.6 and 12.4 mL more than placebo, and the 25 mg result in Study 3 was null: 4.6 mL, 95% CI -1.6 to 10.8, p = 0.15. Onset was within 8 weeks at 25 mg and within 4 weeks at 50 mg, and efficacy was maintained through the 12-week period.
• Funding: industry-funded (sponsor's registration programme reported in the label)

Limit of this finding: Restricting the incontinence analysis to people who were already wetting at baseline makes the trial's incontinence result apply only to that group, not to everyone with an overactive bladder. 'Last observation on treatment' means someone who stopped early is counted at the point they stopped. One result in this block is null: the 25 mg dose in Study 3 did not significantly increase volume voided, with a confidence interval crossing zero.

† For incontinence episodes per 24 hours, the analysis population is restricted to patients with at least 1 episode of incontinence at baseline.

Where the research disagrees

Whether mirabegron raises blood pressure to a degree that matters in practice

• The MYRBETRIQ label (Astellas Pharma US, SPL effective 2024-08-01), section 5.1, rct: MYRBETRIQ/MYRBETRIQ Granules can increase blood pressure. Periodic blood pressure determinations are recommended, especially in hypertensive patients. MYRBETRIQ/MYRBETRIQ Granules is not recommended for use in patients with severe uncontrolled hypertension (defined as systolic blood pressure greater than or equal to 180 mm Hg and/or diastolic blood pressure greater than or equal to 110 mm Hg) (Source 4)
• Lee and colleagues, retrospective observational study of 2,091 Korean patients, 2026, cohort: This study demonstrated that Selebeta® PR is an effective and well-tolerated treatment for adults with OAB, with no clinically meaningful increase in blood pressure and a low incidence of adverse events. (Source 26)

Whether mirabegron is the best-performing beta-3 agonist, now that vibegron is available

• Bai and colleagues, meta-analysis of head-to-head trials, 2025, meta-analysis: Recent data indicated that vibegron demonstrated superior efficacy in reducing urgency and UUI episodes while maintaining a safety profile comparable to mirabegron. Furthermore, vibegron is associated with improved treatment adherence. (Source 17)
• Yajima and colleagues, Bayesian network meta-analysis in men on alpha-1 blockers, 2026, systematic-review: The vibegron node rested on two trials, and no advantage over mirabegron was established; posterior probabilities above 0.8 do not indicate superiority when credible intervals include the null value. (Source 6)

How much

• Reference intake: The dose is set by the prescriber. The label's position for adults with overactive bladder is 25 mg once daily to start, raised if needed to 50 mg once daily after 4 to 8 weeks, alone or with solifenacin 5 mg. (Source 15)
• Upper limit: The label's stated maximum for adults is 50 mg once daily, for monotherapy and for combination with solifenacin alike. (Source 15)
• Studied: Studies 1, 2 and 3 randomised patients to placebo and to mirabegron 25 mg, 50 mg or 100 mg once daily for 12 weeks, with registration numbers NCT00689104, NCT00662909 and NCT00912964. (Source 27)
• Studied: The included population had at least 3 months of symptoms, at least 8 micturitions a day and at least 3 urgency episodes over 3 days, so the trial result applies to people at about that level of symptoms. (Source 28)
• Studied: Healthy volunteers in the overdose experience received single doses up to 400 mg and multiple doses up to 300 mg daily for 10 days. (Source 21)
• Studied: The network meta-analysis compared mirabegron 50 mg against antimuscarinic monotherapies and against solifenacin 5 mg plus mirabegron 25 or 50 mg. (Source 25)

A common belief, and what the research shows

The belief: Mirabegron is the gentler bladder drug, so it has no meaningful side effects and the benefit is large.

What the research shows: It is genuinely gentler on the anticholinergic side effects: the network meta-analysis found it “significantly better tolerated regarding dry mouth, constipation, and urinary retention than 21/22, 9/20, and 7/10 active comparators”. But the benefit is small in absolute terms. On the label's own table the difference from placebo in incontinence episodes per 24 hours was -0.41, -0.34, -0.40 and -0.42, on a baseline of about two and a half to three episodes a day. And it is not side-effect free: hypertension was the most commonly reported adverse reaction, angioedema is described as “Angioedema, associated with upper airway swelling, may be life-threatening.”, and it is a moderate CYP2D6 inhibitor that more than tripled metoprolol exposure in a volunteer study.

Questions and answers

What is it?

Mirabegron is a prescription-only tablet for an overactive bladder, taken once a day as a 25 mg or 50 mg extended-release tablet, with a granule version made up as a liquid for children. It belongs to a class called beta-3 adrenergic agonists, and it was the first of that class licensed for this use. It is not a nutrient or a supplement and has no dietary source. (Source 1)

What does it do in the body?

It switches on beta-3 receptors in the bladder wall, which relaxes the bladder muscle while the bladder is filling. The bladder then holds more urine before it signals urgency, so there are fewer sudden urges, fewer trips to the toilet and fewer wetting episodes. At much higher doses it begins to touch beta-1 receptors as well, which is how it can affect pulse and blood pressure. (Source 1)

Is it good or bad for you?

On the evidence it helps a measurable but modest amount, and the trade-off depends on the person's blood pressure and bladder. The gain is roughly a third to a half of a wetting episode and about half a toilet trip per day better than placebo. Against that sit a measurable rise in blood pressure, hypertension as the commonest reported adverse reaction, and a caution about urinary retention in people with bladder outlet obstruction. It is not recommended at all in severe uncontrolled hypertension. (Source 4)

How do you get more of it?

There is no way to get more of it other than a prescription, and no reason to want more than the label allows. The label's position is 25 mg once daily to start and a maximum of 50 mg once daily, reached after 4 to 8 weeks if needed. Adults can take the tablet with or without food; children should take it with food. (Source 15)

If it is harmful, what reduces it?

If it causes trouble it is stopped, not tapered. The label's own urgent instruction is immediate discontinuation if angioedema affects the tongue, throat or voice box. There is no antidote; the label says treatment of overdose should be symptomatic and supportive, with pulse, blood pressure and ECG monitoring. Because it is a moderate CYP2D6 inhibitor, stopping it also means other medicines it was raising, such as metoprolol, return to their usual levels. (Source 21)

Why might someone be low in it or missing it?

Nobody is naturally short of mirabegron; it is a manufactured drug. The reasons someone with overactive bladder may not be on it are the label's cautions and the way people use it in practice. It is not recommended in severe uncontrolled hypertension, is contraindicated in known hypersensitivity, and in a database of nearly two million people the median time anyone stayed on it was 56 days. (Source 16)

Which whole foods contain it or feed it?

No food contains mirabegron and no food feeds it. Food matters only for how much is absorbed, and the direction differs by age: in adults there were no clinically significant differences with or without food, while in children fasting raised exposure by 120% for the tablet and 170% in peak level for the granules, which is why children are told to take it with food. (Source 12)

What happens if you do not have it?

Overactive bladder itself is not dangerous, so going without the drug means living with the symptoms rather than facing harm. The trial entry criteria describe the level of symptom that was studied: at least 3 months of overactive bladder, at least 8 micturitions a day and at least 3 episodes of urgency over 3 days. The size of what is given up is the absolute difference from placebo, which was well under one episode a day. (Source 28)

How can you test for it?

There is no blood test used to check mirabegron levels in ordinary care. What is monitored instead is the effect: the label asks for periodic blood-pressure measurements, especially in people who already have hypertension, and for ECG and pulse monitoring in overdose. Benefit is judged from a bladder diary, which is what the trials used: a 3-day micturition diary counting episodes and voids per 24 hours. (Source 27)

References

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2. DailyMed (U.S. National Library of Medicine), labeler Astellas Pharma US, Inc.; SPL version effective 2024-08-01. MYRBETRIQ (mirabegron) extended-release tablets - section 14.1, Table 13 caption, column headings and the incontinence-episode rows including the p-value row. 2024. Read the source
3. DailyMed (U.S. National Library of Medicine), labeler Astellas Pharma US, Inc.; SPL version effective 2024-08-01. MYRBETRIQ (mirabegron) extended-release tablets - section 1.1 Adult Overactive Bladder (OAB). 2024. Read the source
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11. DailyMed (U.S. National Library of Medicine), labeler Astellas Pharma US, Inc.; SPL version effective 2024-08-01. MYRBETRIQ (mirabegron) extended-release tablets - section 12.3 Pharmacokinetics, Effect of Alcohol on Mirabegron and in vitro effect of mirabegron on other drugs. 2024. Read the source
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13. DailyMed (U.S. National Library of Medicine), labeler Astellas Pharma US, Inc.; SPL version effective 2024-08-01. MYRBETRIQ (mirabegron) extended-release tablets - section 6.1 Clinical Trials Experience, Study 4 neoplasm reports and the Japanese Stevens-Johnson syndrome case. 2024. Read the source
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15. DailyMed (U.S. National Library of Medicine), labeler Astellas Pharma US, Inc.; SPL version effective 2024-08-01. MYRBETRIQ (mirabegron) extended-release tablets - section 2.2 Recommended Dosage for Adult Patients with OAB. 2024. Read the source
16. European Urology Open Science. Treatment Persistence and Adherence with Overactive Bladder Medications in Taiwan: A Retrospective Database Analysis.. 2026. PMID 42058870, DOI 10.1016/j.euros.2026.03.020. Read the source
17. Medicine. An updated meta-analysis of head-to-head trials comparing the efficacy, safety, and adherence of mirabegron and vibegron in overactive bladder.. 2025. PMID 41366890, DOI 10.1097/MD.0000000000046109. Read the source
18. DailyMed (U.S. National Library of Medicine), labeler Astellas Pharma US, Inc.; SPL version effective 2024-08-01. MYRBETRIQ (mirabegron) extended-release tablets - section 6.1 Clinical Trials Experience, monotherapy adverse reaction table. 2024. Read the source
19. DailyMed (U.S. National Library of Medicine), labeler Astellas Pharma US, Inc.; SPL version effective 2024-08-01. MYRBETRIQ (mirabegron) extended-release tablets - section 5.2 Urinary Retention in Patients with Bladder Outlet Obstruction and in Patients Taking Muscarinic Antagonist Medications for OAB. 2024. Read the source
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21. DailyMed (U.S. National Library of Medicine), labeler Astellas Pharma US, Inc.; SPL version effective 2024-08-01. MYRBETRIQ (mirabegron) extended-release tablets - section 10 OVERDOSAGE. 2024. Read the source
22. DailyMed (U.S. National Library of Medicine), labeler Astellas Pharma US, Inc.; SPL version effective 2024-08-01. MYRBETRIQ (mirabegron) extended-release tablets - section 5.1 Increases in Blood Pressure, Increases in Blood Pressure in Pediatric Patients 3 Years and Older. 2024. Read the source
23. DailyMed (U.S. National Library of Medicine), labeler Astellas Pharma US, Inc.; SPL version effective 2024-08-01. MYRBETRIQ (mirabegron) extended-release tablets - section 14.1, continuation of Table 13: micturition-frequency and volume-voided rows with p-values, the table's four footnotes, and the onset-and-maintenance sentences. Its caption and column headings are in dailymed-mirabegron-studies, which this block follows directly. 2024. Read the source
24. European Urology. Efficacy and Tolerability of Mirabegron Compared with Antimuscarinic Monotherapy or Combination Therapies for Overactive Bladder: A Systematic Review and Network Meta-analysis.. 2018. PMID 29699858, DOI 10.1016/j.eururo.2018.03.020. Read the source
25. European Urology. Efficacy and Tolerability of Mirabegron Compared with Antimuscarinic Monotherapy or Combination Therapies for Overactive Bladder: A Systematic Review and Network Meta-analysis.. 2018. PMID 29699858, DOI 10.1016/j.eururo.2018.03.020. Read the source
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27. DailyMed (U.S. National Library of Medicine), labeler Astellas Pharma US, Inc.; SPL version effective 2024-08-01. MYRBETRIQ (mirabegron) extended-release tablets - section 14.1, trial design, entry criteria and endpoints. 2024. Read the source
28. DailyMed (U.S. National Library of Medicine), labeler Astellas Pharma US, Inc.; SPL version effective 2024-08-01. MYRBETRIQ (mirabegron) extended-release tablets - section 14.1, trial population and entry criteria. 2024. Read the source