Long‐acting glucagon‐like peptide 1 receptor agonists boost erectile function in men with type 2 diabetes mellitus complaining of erectile dysfunction: A retrospective cohort study

Abstract Introduction The pharmacological management of erectile dysfunction (ED) in type 2 diabetes (T2D) is challenging as ED has a multifactorial etiology. The therapeutic potential of certain antihyperglycemic medications, such as glucagon‐like peptide 1 receptor agonists (GLP‐1RAs), has yet to be entirely studied in this setting. Material and methods A retrospective cohort study was conducted on 108 outpatients (median age 60 [56, 65] years) with T2D complaining of ED. Data were extracted from a database referring to patients with a 1‐year follow‐up on stable treatment with metformin alone ( n = 45) and GLP‐1RAs as an add‐on to metformin ( n = 63). Erectile function was assessed by the 5‐item International Index of Erectile Function (IIEF5) at baseline and after 1 year of stable treatment . Values were compared between baseline (T0) and after 12 months of treatment (T12). Results ED was confirmed in all at baseline, with an IIEF5 score range between 13 and 19 points. After 12 months of treatment, glucose management was better in patients treated with GLP‐1RAs plus metformin (HbA1c T0: 8.3 ± 0.2 vs. HbA1c T12: 7% ± 0.3%, p < 0.0001) than in those on metformin alone (HbA1c T0: 7 ± 0.5 vs. HbA1c T12: 7.3 ± 0.4, p = 0.0007). GLP‐1RAs plus metformin over metformin alone 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 the IIEF5 score was more relevant in patients with higher baseline IIEF5 score (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). The leading determinant of the final IIEF5 score was a 1‐year treatment with GLP‐1RAs plus metformin over metformin alone (2.74 ± 0.53, p < 0.0001). Discussion GLP‐1RAs plus metformin over metformin alone improved ED regardless of different background characteristics of patients and partially irrespective of therapeutic targets achieved after 12 months of treatment. GLP‐1RAs may have induced positive vasculature effects, resulting in improved erectile function in T2D. Conclusion Due to the retrospective nature of the study, a potential cause–effect relationship between the use of GLP‐1RAs plus metformin over metformin alone in improving ED cannot be verified and confirmed. Randomized clinical trials are needed to provide evidence supporting the use of GLP‐1RAs for treating ED in T2D.