Glucagon-Like Peptide-1 Receptor Agonists May Stave Off Prostate Surgery for Men Treated with 5-Alpha Reductase Inhibitors

Emerging real-world evidence suggests that glucagon-like peptide-1 (GLP-1) receptor agonists may augment the therapeutic effects of 5-alpha reductase inhibitors (5-ARIs) in patients with benign prostatic hyperplasia (BPH). Data from a nationwide claims database, presented at the 2026 Annual Meeting of the American Urological Association in Washington, D.C., showed that taking GLP-1 agonists alongside 5-ARIs may decrease the risk of surgical intervention in patients with BPH. 

Metabolic syndrome and systemic inflammation have been shown to accelerate BPH progression through interrelated pathways that promote prostate enlargement and worsening urinary symptoms. In the modern clinical context, many men with BPH may be treated with medications such as alpha-blockers or 5-ARIs for lower urinary tract symptoms while also taking GLP-1 receptor agonists for metabolic dysfunction. 

Recent research has shown that GLP-1 receptors are present in non-malignant and malignant prostatic tissues. While the effects of GLP-1 agonists on the prostate are not fully understood, they likely block oncogenic signaling pathways and cellular proliferation, potentially shrinking the prostate volume beyond what 5-ARIs can achieve on their own. “Knowing there are GLP-1 receptors on the prostate, we sought to investigate if their use could be associated with progression of disease in BPH,” lead author Devin Dishong, a third-year medical student at the Johns Hopkins University School of Medicine, said in an interview. “Perhaps, GLP-1 agonists acting on the prostate can alter response to 5-ARI by enhancing receptor binding and signaling. Further laboratory research is warranted to fully understand this potential relationship.” 

Dishong and colleagues reviewed nationwide claims collected between 2017 and 2022 from men aged 40 to 75 years who were receiving monotherapy or combination therapy for BPH. The analysis included more than 17,000 patients treated with alpha-blockers for BPH-related symptoms, as well as 807 patients treated with 5-ARIs and 6,257 who were using combination therapy. Patients with prior prostatectomy or BPH surgery were excluded. 

The results showed that patients actively using GLP-1 agonists while on 5-ARI therapy demonstrated a statistically significant reduction in the risk of requiring BPH-related surgery at 3- and 5-year follow-up intervals. However, the reduced risk of surgical intervention was observed only in patients using 5-ARIs alone. Men treated with alpha-blockers alone did not show a statistically significant difference in surgical rates whether they used GLP-1 agonists or not. “The fact the 5-ARI/GLP-1 group only, and not the alpha-blocker/GLP-1 group, showed a reduction in progression to BPH surgery is an interesting finding,” Dishong said. “A potential explanation is that GLP-1 agonists may, in synergy with 5-ARIs, act to reduce prostate tissue size, whereas alpha-blockers have no direct effect on prostate tissue size.” 

By contrast, participants who were on combination therapy for BPH and GLP-1 receptor agonists had an increased risk of requiring BPH surgery at 3 and 5 years. While GLP-1 use was associated with a reduced risk for urinary retention and urinary tract infections in both monotherapy groups, this effect was not significant in patients receiving combination therapy. 

“Due to the inherent limitations of conducting a retrospective database study, this data should not be interpreted as causal,” Dishong noted. “However, there are several possible explanations for our findings. First, patients on combination therapy may likely already have more severe BPH, which makes them more likely to undergo surgical intervention inherently. A natural follow-up question would be asking why the benefit of 5-ARIs was not observed in the combination group since these patients are also receiving 5-ARIs. Perhaps the patients who are on combination therapy already have such advanced disease that the potential therapeutic effect of GLP-1 augmentation of 5-ARI activity is limited, known as a ceiling effect, and surgery is the preferred option - for which GLP-1s make patients more attractive surgical candidates.” 

While the results of the retrospective analysis hint to the potential synergistic benefits of combining GLP-1 agonists and 5-ARIs, these findings may not make their way into the clinical guidelines just yet. Nevertheless, providers may use this insight to personalize treatment plans for men with BPH and metabolic dysfunction. 

“We believe it is premature to recommend the off-label use of GLP-1 agonists solely for the management of BPH based on retrospective data,” the author added. “However, our study does have implications for the multidisciplinary management of patients with comorbid conditions. For patients presenting with BPH who also have established indications for GLP-1 agonist therapy, our data suggest that using a GLP-1, particularly in conjunction with a 5-ARI, could provide a dual benefit by concurrently addressing metabolic needs and potentially slowing BPH disease progression. Furthermore, these results encourage urologists, endocrinologists, and primary care providers to collaborate more closely when selecting antidiabetic or weight-management pharmacotherapy for men with enlarged prostates. Ultimately, we hope this foundational work serves as a catalyst for prospective, randomized clinical trials that could formally evaluate GLP-1 agonists as an adjunct therapy in standard BPH clinical pathways.”