The Shift in Incontinence Treatment: Beyond Traditional Medications
For decades, treatment for urge incontinence—the sudden, intense urge to urinate—has centered on anticholinergic drugs like oxybutynin and tolterodine. While effective for many, these medications are often associated with side effects such as dry mouth, constipation, and blurred vision, which can lead to patients discontinuing treatment. This has fueled the search for more tolerable and effective alternatives. More recent advancements have focused on different mechanisms of action, offering new hope for those struggling with bladder control issues.
Gemtesa (Vibegron): A Newer Oral Option for Urge Incontinence
One of the most significant recent developments in the pharmacological management of overactive bladder (OAB) is the drug Gemtesa (vibegron). Approved by the U.S. Food and Drug Administration (FDA) in December 2020, Gemtesa represents a new class of oral medication, the beta-3 adrenergic receptor agonists.
How Gemtesa Works
Unlike anticholinergics that block bladder muscle contractions, Gemtesa works by activating the beta-3 adrenergic receptors found on the bladder muscle. This activation causes the bladder muscle to relax, increasing the bladder's capacity to hold urine and reducing involuntary contractions. The result is a decrease in the key symptoms of OAB, including:
- Urge urinary incontinence (leakage episodes)
- Urgency (the sudden need to urinate)
- Frequency (urinating often)
Clinical Trial Data
The FDA's approval of Gemtesa was based on the 12-week EMPOWUR study, which demonstrated significant reductions in daily urge urinary incontinence (UUI), micturition (urination) frequency, and urgency episodes compared to a placebo. In 2025, the FDA expanded its approval for men with OAB symptoms, including urinary incontinence, who are already being treated for benign prostatic hyperplasia (BPH). This expanded indication addresses an important area of unmet need in male bladder health.
Notable Side Effects
Gemtesa is generally well-tolerated, and unlike older anticholinergic drugs, it is not associated with side effects like dry mouth or constipation. The most common adverse effects observed in clinical trials included headache, nasopharyngitis, diarrhea, and nausea. The drug also demonstrated rates of hypertension and increased blood pressure similar to placebo in the EMPOWUR study.
Investigational Drugs and Emerging Therapies for Stress Incontinence (SUI)
While Gemtesa addresses urge incontinence, stress urinary incontinence (SUI)—leakage triggered by physical movement like coughing or sneezing—has seen slower progress in pharmacological treatment. The current medication options for SUI are limited, which has prompted research into novel drugs.
TAS-303
An investigational medication, TAS-303, has shown promising results in recent clinical trials for women with SUI. As a highly selective noradrenaline reuptake inhibitor, TAS-303 works by increasing pressure within the urethra, which can lessen bladder leakage. This drug is different from the dual serotonin and noradrenaline reuptake inhibitor duloxetine, which is approved for SUI in some countries but has more significant side effects. Trial results reported in 2024 indicated that TAS-303 led to a significant reduction in incontinence episodes with a better safety profile than duloxetine.
mRNA Therapy (VMB-100)
Another cutting-edge approach for SUI is an investigational mRNA therapy called VMB-100. Developed by the company Versameb, this therapy is designed to be injected locally into the urinary sphincter muscle to help regenerate muscle function. Preclinical studies have shown that it accelerates the regeneration of the urinary sphincter, and a Phase IIa clinical trial was authorized by the FDA to begin in 2024. This represents a potential first-in-class mRNA therapy that could address the root cause of muscle weakness in SUI.
Comparison of Incontinence Medications
| Feature | Gemtesa (Vibegron) | Anticholinergics (e.g., Oxybutynin, Tolterodine) | TAS-303 (Investigational) |
|---|---|---|---|
| Type of Incontinence | Urge Incontinence (OAB) | Urge Incontinence (OAB) | Stress Incontinence (SUI) |
| Mechanism of Action | Beta-3 adrenergic agonist; relaxes bladder muscle | Blocks nerve signals that trigger bladder contractions | Selective noradrenaline reuptake inhibitor; increases urethral pressure |
| FDA Status | Approved for OAB in adults (including men with BPH) | Approved for OAB | Phase 2 clinical trials in women |
| Common Side Effects | Headache, diarrhea, nausea, URT infection | Dry mouth, constipation, blurry vision, confusion | Mild or moderate; avoids CNS/GI side effects of similar drugs |
| Drug Delivery | Once-daily oral tablet | Oral tablets, extended-release, patch, gel | Likely an oral tablet, based on trial |
Other Emerging Treatment Options
Beyond new drug compounds, other innovative therapies are emerging to combat incontinence, particularly for those who do not respond well to medications.
Implantable Devices
For instance, the Altaviva device, an implantable tibial neuromodulation system, was approved by the FDA in September 2025 for urge urinary incontinence. This device is implanted near the ankle and sends electrical pulses to stimulate nerves involved in bladder control. This offers a long-term solution for patients without the need for daily medication and its associated side effects.
Botulinum Toxin Injections
Botox injections into the bladder muscle are another established treatment for urge incontinence, particularly when other medications have failed. The injections work by paralyzing the bladder muscle to prevent involuntary contractions. While not a new treatment, it remains a valuable option for certain patients, with effects lasting for several months.
Conclusion: The Evolving Landscape of Incontinence Therapy
While older drug classes like anticholinergics still have a role, recent advances have significantly diversified the treatment landscape for urinary incontinence. Gemtesa (vibegron) offers a well-tolerated oral alternative for urge incontinence by acting on different receptors, while investigational drugs like TAS-303 and novel approaches like mRNA therapy show promise for stress incontinence. Alongside pharmacological options, innovative devices such as the Altaviva implant offer new possibilities for long-term management. These developments signify a shift toward more personalized and effective treatments, with a continued focus on improving patient quality of life. For anyone experiencing incontinence, a consultation with a healthcare provider is essential to determine the best therapeutic path, which may now include newer, more targeted options. For more information on the pharmacological management of incontinence, consult authoritative medical resources such as those from the National Institutes of Health.
