Established and emerging treatments for diabetes-associated lower urinary tract dysfunction

Abstract

Dysfunction of the lower urinary tract (LUT) including urinary bladder and urethra (and prostate in men) is one of the most frequent complications of diabetes and can manifest as overactive bladder, underactive bladder, urinary incontinence, and as aggravated symptoms of benign prostate hyperplasia. We have performed a selective literature search to review existing evidence on efficacy of classic medications for the treatment of LUT dysfunction in diabetic patients and animals, i.e., α1-adrenoceptor and muscarinic receptor antagonists, β3-adrenoceptor agonists, and phosphodiesterase type 5 inhibitors. Generally, these agents appear to have comparable efficacy in patients and/or animals with and without diabetes. We also review effects of antidiabetic medications on LUT function. Such studies have largely been performed in animal models. In the streptozotocin-induced models of type 1 diabetes, insulin can prevent and reverse alterations of morphology, function, and gene expression patterns in bladder and prostate. Typical medications for the treatment of type 2 diabetes have been studied less often, and the reported findings are not yet sufficient to derive robust conclusions. Thereafter, we review animal studies with emerging medications perhaps targeting diabetes-associated LUT dysfunction. Data with myoinositol, daidzein, and with compounds that target oxidative stress, inflammation, Rac1, nerve growth factor, angiotensin II receptor, serotonin receptor, adenosine receptor, and soluble guanylyl cyclase are not conclusive yet, but some hold promise as potential treatments. Finally, we review nonpharmacological interventions in diabetic bladder dysfunction. These approaches are relatively new and give promising results in preclinical studies. In conclusion, the insulin data in rodent models of type 1 diabetes suggest that diabetes-associated LUT function can be mostly or partially reversed. However, we propose that considerable additional experimental and clinical studies are needed to target diabetes itself or pathophysiological changes induced by chronic hyperglycemia for the treatment of diabetic uropathy.

Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder

“…There are currently multiple pharmacological options to treat diabetes-induced bladder dysfunctions, notably using α 1 -adrenoceptor and muscarinic receptor antagonists, β 3 -adrenoceptor agonists and phosphodiesterase type 5 inhibitors [ 72 ]. However, here also, newer treatments and drugs are needed to improve long-term efficacy.…”

Association of diabetes, hypertension, and their combination with basal symptoms and treatment responses in overactive bladder patients

“…From a treatment perspective it possibly is more relevant that presence of one or two comorbidities were associated with attenuated treatment responses, but the degree of attenuation was small. Considering that there are no specific treatments for lower urinary tract dysfunction with comorbidities such as diabetes ( Erdogan et al, 2022 ), existing OAB medications remain the best treatment option even if comorbidities are present. Therefore, we consider the present findings to be of pathophysiological and pharmacological interest but propose that they do not justify changing existing paradigms for the clinical management of OAB.…”

“…However, little clinical data are available in this regard. There is also limited data on the question whether the combined presence of diabetes and hypertension affects therapeutic outcomes in OAB patients ( Erdogan et al, 2022 ). Therefore, we have used data from two large non-interventional studies in OAB patients ( Amiri et al, 2021 ) to explore the association of diabetes, hypertension and their combination with baseline symptoms of OAB patients and their effect on therapeutic outcomes in a clinically meaningful way under real-world conditions.…”

The impact of diabetes on overactive bladder presentations and associations with health-seeking behavior in China, South Korea, and Taiwan: Results from a cross-sectional, population-based study

“…31,32 Currently, pharmacotherapy specific to the pathophysiology of DBD, such as mirabegron, may provide potentially effective treatments for these patients. 1,32…”

“…29,30 Healthcare providers need to be sensitive in evaluating and discussing UI with patients, since lifestyle modification and behavior therapy with or without pharmacotherapy may help to improve symptoms. 31,32 Currently, pharmacotherapy specific to the pathophysiology of DBD, such as mirabegron, may provide potentially effective treatments for these patients. 1,32 In addition, we observed that the symptom of urgency is not a predictor of treatment-seeking in this study.…”