- Prior data are mixed regarding the possible association between GLP-1 drugs and erectile dysfunction (ED), a common problem in men with diabetes.
- This real-world study of men with type 2 diabetes identified a potentially modest link between GLP-1 agonist use and ED compared to GLP-4 inhibitors.
- Researchers called for randomized trials using standardized ED assessments to explore any potential associations.
A TARGET trial simulation suggests that the use of GLP-1 receptor agonists may be associated with a modest increase in erectile dysfunction (ED) risk in men with type 2 diabetes.
Using US electronic health record data, the incidence of ED diagnosis over approximately 3 years of follow-up was 26% higher among new users of GLP-1 drugs than among DPP-4 inhibitor initiators (35.2 vs. 28 per 1,000 person-years; HR 1.26, 95% CI 1.08–1.46, P=0.004), Yong Chen, PhD, of the University of Pennsylvania in Philadelphia, and colleagues reported.
The association was generally consistent across demographic and clinical subgroups, but lost significance in a sensitivity analysis aimed to capture unmeasured confounding or systematic biases (HR 1.23, 95% CI 0.86-1.75), according to the study eClinicalMedicine.
Furthermore, the results contradict earlier data and should be considered hypothesis-generating because they “may reflect residual or selection bias,” Chen and colleagues wrote. “Future randomized controlled trials with standardized assessment of erectile function and comprehensive longitudinal measurement of treatment exposure are needed to confirm these findings and clarify the underlying mechanisms.”
ED affects about 50% of men with type 2 diabetes at some point in their lifetime. The pathophysiology is multifactorial, the researchers explained, “primarily attributed to endothelial dysfunction, impaired nitric oxide signaling, and autonomic neuropathy, which collectively contribute to vascular and neurogenic deficits.”
The relationship between the use of GLP-1 agonists and ED is “complex,” he said, with some preclinical and clinical data suggesting potential erection health benefits.
For example, an exploratory analysis of the randomized REWIND trial found that slightly fewer men in the group given dulaglutide (Trulicity) developed erectile dysfunction compared with the placebo group during a median follow-up of more than 5 years (HR 0.92, 95% CI 0.85–0.99). P=0.021).
Meanwhile, a cohort study Using the TrinetX database, an increase in the use of PDE5 inhibitors such as sildenafil (Viagra) was reported in non-diabetic men prescribed semaglutide (Ozempic, Vegovy) with higher ED risk and obese non-diabetic men compared to non-users.
Chen and colleagues said, “These conflicting findings between real-world evidence and trial-based data underscore the need for further mechanistic and prospective studies to clarify the net effect of GLP-1 receptor agonists on sexual health.”
Their target testing simulation used the University of Pennsylvania Health System’s electronic health records from January 2019 to September 2024. Adult men with type 2 diabetes identified by diagnostic code were included. Men with a prior ED diagnosis or end-stage renal disease were excluded.
After constant inverse probability of treatment weighting, the analysis included 4,910 patients who started a GLP-1 drug and 5,524 who started a DPP-4 inhibitor. The mean age was 63, body mass index was 32.8, 55% were white, and 23% were black. Before weight loss, GLP-1 drug users were younger, had a higher prevalence of obesity, and had a higher estimated glomerular filtration rate.
Analyzes stratified by specific GLP-1 agent showed higher ED risk in men prescribed dulaglutide (HR 1.44, 95% CI 1.20–1.73). Estimates for the other agents—semaglutide, tirazepate (Mounjaro, Zepbound), and liraglutide (Victoza, Saxenda)—were modest or imprecise due to small sample sizes.
Chen and co-authors also used US electronic health record data from the TriNetX database to validate their findings. In this analysis, men using GLP-1 drugs had a 13% increased ED risk compared with DPP-4 inhibitor users over approximately 3 years (HR 1.13, 95% CI 1.10-1.17, P<0.001).
The researchers acknowledged some limitations, including a lack of data on changes in body weight and glycemic control after starting treatment, as well as pre-baseline medication history and diabetes duration. Furthermore, ED was identified using diagnosis codes, which may not capture mild cases and may introduce misclassification.
