Endocrine Abstracts

Background: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are proven to boost serum testosterone levels in men with type 2 diabetes (T2D) and functional hypogonadism. Nevertheless, the therapeutic potential of this class of drugs on erectile dysfunction (ED) has yet to be entirely studied in men with T2D and functional hypogonadism.

Methods: A retrospective cohort study was conducted on 108 outpatients (60 [56, 65] years) with T2D and complaining of ED. Data were extracted from the database referring to patients with a 1-year follow-up on stable treatment with metformin alone (M, n=45) and GLP-1RAs as an add-on to metformin (GLP-1RA+M, n=63). Erectile function was assessed by the 5-item International Index of Erectile Function (IIEF5) at baseline and after 1 year of treatment. Values were compared between baseline (T0) and after 12 months of treatment (T12).

Results: ED was confirmed at baseline in all (IIEF5 score 13 to 19 points). After 12 months of treatment, glucose management was better in patients on GLP-1RAs+M (HbA1c T0: 8.3±0.2 vs HbA1c T12: 7%±0.3%, P<0.0001) than in those on M (HbA1c T0: 7±0.5 vs HbA1c T12: 7.3±0.4, P= 0.0007). GLP-1RAs+M over M resulted in a significant weight loss (-5.82±0.69 kg, P<0.0001), reduction in waist circumference (-4.99±0.6 cm, P<0.0001), improvement in HbA1c (-0.56%±0.13%, P<0.0001), and fasting plasma glucose (-25.54±3.09 mg/dl, P<0.0001), increase in total (+41.41±6.11 ng/dl, P<0.0001) and free (0.44±0.09 ng/dl, P<0.0001) testosterone levels, and gain in self-reported erectile function (IIEF5 score: +2.26±0.26, P<0.0001). The gain in IIEF5 scores was more relevant in patients with higher baseline IIEF5 (estimated coefficient: 0.16±0.08, P= 0.045), those having carotid stenosis (0.50±0.24, P= 0.045), and showing weight loss from baseline (-0.08±0.03, P= 0.013), regardless of serum testosterone. The leading determinant of the final IIEF5 score was a 1-year treatment with GLP-1RAs+M over M (2.74±0.53, P<0.0001).

Conclusions: GLP-1RAs+M over M improved ED regardless of different background characteristics and testicular function of T2D patients and partially irrespective of therapeutic targets achieved after 12 months of treatment. Controlled trials are needed to confirm if GLP-1RAs have direct and helpful vasculature effects boosting erectile function in T2D.