The retrospective cohort study analyzed data from the TriNetX global health research network, covering the period from May 2022 to May 2025. The study population consisted of male patients aged between 18 and 70 years, all diagnosed with T2D and with no prior history of erectile dysfunction. Researchers conducted three separate 1:1 propensity score-matched comparisons between tirzepatide and sitagliptin, injectable semaglutide, and dulaglutide.
The primary outcome assessed was a diagnosis of erectile dysfunction or the initiation of phosphodiesterase type 5 (PDE-5) inhibitor therapy, which is commonly used to treat ED.
The study yielded the following notable results:
- Tirzepatide use was associated with a significantly reduced risk of erectile dysfunction across all comparisons.
- Men treated with tirzepatide were 30% less likely to develop erectile dysfunction compared to those on sitagliptin (RR: 0.70).
- The risk of erectile dysfunction was 33% lower in tirzepatide users compared to those on semaglutide (RR: 0.67).
- Compared to dulaglutide, tirzepatide was linked with a 45% lower risk of erectile dysfunction (RR: 0.55).
- All comparisons showed statistically significant results.
According to the authors, the investigation is the first to examine the relationship between tirzepatide use and incident ED in men with type 2 diabetes. The authors suggest that tirzepatide’s superior metabolic benefits—such as improved glycemic control and greater weight loss—could play a critical role in enhancing vascular and neurohormonal health, thereby reducing ED risk.
Sitagliptin, a DPP-4 inhibitor, has not previously been linked with ED risk reduction. Thus, the contrast highlights the broader physiological benefits of tirzepatide. The study highlights that the metabolic improvements associated with tirzepatide may have downstream effects on erectile function, a key quality-of-life concern for many men with T2D.
The authors advocate for future randomized controlled trials to validate their findings and to further investigate the underlying mechanisms, especially the vascular, hormonal, and neurogenic pathways that might mediate the effect of tirzepatide on erectile function. Additionally, they recommend exploring whether there is a differential response to PDE-5 inhibitors in patients already on GLP-1 receptor agonist therapy.
The authors concluded, "The study adds to the growing body of evidence supporting the expanded benefits of tirzepatide in diabetes management, suggesting that its use may not only improve glycemic and weight outcomes but also positively impact sexual health in men."
Reference:
Cowart, K., Murphy, C., & Carris, N. (2025). Association of tirzepatide with erectile dysfunction in people with type 2 diabetes. Journal of Diabetes and its Complications, 39(10), 109116. https://doi.org/10.1016/j.jdiacomp.2025.109116
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