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Review
. 2021 Jun 5;10(11):2501.
doi: 10.3390/jcm10112501.

Role of Glucose-Lowering Medications in Erectile Dysfunction

Angelo Cignarelli  1 , Valentina Annamaria Genchi  1 , Rossella D'Oria  1 , Fiorella Giordano  1 , Irene Caruso  1 , Sebastio Perrini  1 , Annalisa Natalicchio  1 , Luigi Laviola  1 , Francesco Giorgino  1
Affiliations
Review

Role of Glucose-Lowering Medications in Erectile Dysfunction

Angelo Cignarelli et al. J Clin Med. .

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.

Keywords: diabetes; erectile dysfunction; glucose-lowering medications.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Effects of hyperglycaemia and hypogonadism on endothelial cell and CCSMC dysfunction. AGE, advanced glycation end-product; CCSMCs, corpus cavernosum smooth muscle cells; cGMP, cyclic GMP; eNOS, endothelial nitric oxide synthase; NO, nitric oxide.
Figure 2
Figure 2
Principal glucose-lowering agents and their downstream pathways that could restore the relaxation of CCSMC and promote erectile function in a diabetic setting. AGE, advanced glycation end-product; AMPD, AMP deaminase; KATP; ATP-sensitive potassium channel; CCSMC, corpus cavernosum smooth muscle cell; cGMP, cyclic GMP; eNOS, endothelial nitric oxide synthase; GLP-1RA, GLP-1 receptor agonist; I4, SU compound; IGF-IR, insulin-like growth factor I receptor; MYPT1, myosin phosphatase target subunit 1; nNOS, neuronal nitric oxide synthase; NO, nitric oxide; PECAM-1, platelet endothelial cell adhesion molecule; ROS, reactive oxygen species, SGLT2i, sodium–glucose cotransporter-2 inhibitor; SUs, sulfonylureas; TZDs, thiazolidinediones. ↓ decrease, ↑ increase.
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