Role of Glucose-Lowering Medications in Erectile Dysfunction

Abstract

Erectile dysfunction (ED) is a long-term complication of type 2 diabetes (T2D) widely known to affect the quality of life. Several aspects of altered metabolism in individuals with T2D may help to compromise the penile vasculature structure and functions, thus exacerbating the imbalance between smooth muscle contractility and relaxation. Among these, advanced glycation end-products and reactive oxygen species derived from a hyperglycaemic state are known to accelerate endothelial dysfunction by lowering nitric oxide bioavailability, the essential stimulus of relaxation. Although several studies have explained the pathogenetic mechanisms involved in the generation of erectile failure, few studies to date have described the efficacy of glucose-lowering medications in the restoration of normal sexual activity. Herein, we will present current knowledge about the main starters of the pathophysiology of diabetic ED and explore the role of different anti-diabetes therapies in the potential remission of ED, highlighting specific pathways whose activation or inhibition could be fundamental for sexual care in a diabetes setting.

Adipose Tissue Dysfunction and Obesity-Related Male Hypogonadism

“…Indeed, one in five adults are predicted to have obesity by 2025 [ 1 ]. Obesity is also one of the key risk factors for many noncommunicable diseases, such as coronary heart disease, hypertension and stroke, certain types of cancer, type 2 diabetes, gallbladder disease, dyslipidemia, osteoarthritis and gout, and pulmonary diseases, including sleep apnea, and represents one of the principal causes of secondary hypogonadism in men, a condition characterized by the impairment of the hypothalamic–pituitary–testicular (HPT) axis, in which the reduction in testosterone levels is also accompanied by signs and symptoms of hypogonadism, such as decreases in libido, erectile function, semen quality, strength, and mood [ 2 , 3 , 4 , 5 , 6 ]. The prevalence of hypogonadism in normal-weight adult males is around 32%, while about 75% of subjects with severe obesity (BMI > 40 kg/m 2 ) have from hypogonadism [ 7 , 8 , 9 , 10 ].…”

The Role of Antihyperglycemic Drugs and Diet on Erectile Function: Results from a Perspective Study on a Population with Prediabetes and Diabetes

“…Considering the effect of antidiabetic treatment on erectile function (EF), a limited number of studies focused on humans are available [ 12 , 13 , 14 ], so the data are still limited on ED. A study conducted on Metformin use in diabetic men with ED showed an increased International Index of Erectile Function (IIEF) score after treatment [ 15 ].…”

Accidental exposure to glimepiride from adulterated medication resulting in severe hypoglycaemia

“…This study reports the second of two life-threatening episodes of hypoglycaemia followed by unintentional self-poisoning with glimepiride in this patient. Concurrent alcohol ingestion may have accentuated the risk through the inhibition of glycogenolysis ( 6 ). Without the use of a sulphonylurea assay, this patient may have been subject to invasive intraabdominal ultrasound or hazardous partial pancreatectomy.…”

“…A likely explanation for the remoteness of the ‘Tadapox’ consumption from the hypoglycaemic event is the consumption of alcohol. Alcohol is known to reduce hepatic gluconeogenesis and glycogenolysis, limiting the efficacy of counter-regulatory responses in starvation states or hypoglycaemia ( 5 , 6 ).…”

“…Furthermore, alcohol can inhibit hepatic metabolism of glimepiride, prolonging its duration of action ( 6 ).…”