GLP-1 Receptor Agonists Linked to Mild Erectile Dysfunction Risk: The Lancet
USA: Prior evidence on the association between GLP-1 receptor agonists and erectile dysfunction (ED) in men with type 2 diabetes has been inconsistent. Researchers have found in a new real-world study that there was a modest increase in ED risk among men using GLP-1 agonists compared with those on DPP-4 inhibitors. However, the observed association is small and does not establish causality.
The authors emphasize the need for randomized controlled trials with standardized ED assessment tools to better clarify this potential relationship.
The study published in eClinicalMedicine by Huilin Tang and colleagues from the University of Pennsylvania Perelman School of Medicine explores the potential association between GLP-1 receptor agonists (GLP-1RAs) and erectile dysfunction in men with type 2 diabetes, an area where evidence has remained limited.
The researchers conducted a target trial emulation using electronic health records from a large U.S. health system between January 2019 and September 2024. The study included adult men with T2D initiating either GLP-1RAs or dipeptidyl peptidase-4 inhibitors (DPP-4is), with new-onset erectile dysfunction identified through diagnostic codes as the primary outcome.
To ensure balanced comparisons, stabilized inverse probability of treatment weighting was used to align baseline characteristics. Cox proportional hazards models were applied to estimate risk, with additional subgroup analyses, sensitivity testing, and external validation performed to confirm the robustness of the findings.
The following were the key findings:
- The adjusted analysis included 4,910 men initiating GLP-1 receptor agonists and 5,524 men starting DPP-4 inhibitors, with comparable baseline characteristics.
- The incidence of erectile dysfunction was higher among GLP-1RA users at 35.2 cases per 1,000 person-years.
- In comparison, DPP-4 inhibitor users had an incidence rate of 28.0 cases per 1,000 person-years.
- GLP-1RA use was associated with a modestly increased risk of erectile dysfunction, with a hazard ratio of 1.26.
- The association remained consistent across multiple subgroup and sensitivity analyses.
- Similar findings were observed in an external validation cohort.
- After applying additional calibration to address potential residual bias, the association was attenuated.
- The association was no longer statistically significant after this adjustment.
- These findings suggest that unmeasured confounding factors may have influenced the observed results.
The authors caution that these findings should be interpreted carefully, as observational studies cannot establish a direct cause-and-effect relationship. They note that the modest increase in ED risk may reflect underlying differences in patient characteristics or treatment selection rather than a true pharmacological effect.
Overall, the study highlights the importance of considering sexual health outcomes in men with type 2 diabetes receiving GLP-1 receptor agonists. While these drugs remain highly effective for metabolic and cardiovascular management, further research, particularly randomized controlled trials, is needed to better understand any potential impact on erectile function and the biological mechanisms involved.
Reference:
Tang, H., Lu, Y., Zhang, B., Zhang, D., Asch, D. A., & Chen, Y. (2026). GLP-1 receptor agonist and risk of erectile dysfunction in men with type 2 diabetes: A target trial emulation. EClinicalMedicine, 94, 103857. https://doi.org/10.1016/j.eclinm.2026.103857
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