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.
Keywords: erectile dysfunction; glucagon-like peptide 1 receptor agonists; international index of erectile function; retrospective cohort study; type 2 diabetes.
© 2023 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.