TOPLINE:

SGLT2 inhibitor use was associated with a significantly lower risk for androgen deprivation therapy (ADT) failure and next-generation hormonal agent failure in men with prostate cancer. SGLT2 inhibitor use also showed a trend toward improved survival outcomes, but the findings did not reach statistical significance.

METHODOLOGY:

• Early evidence suggests that SGLT2 inhibitors may have antitumor effects, but it’s unclear whether these antidiabetic drugs can improve outcomes in patients with prostate cancer.
• To evaluate the potential link, researchers conducted a population-based, sequential target trial emulation using territory-wide electronic health records from Hong Kong Hospital Authority, covering 7.5 million people from January 1993 to April 2025. The analysis included 14,223 men (median age, 74 years) with prostate cancer who received SGLT2 inhibitors during ADT. Patients not receiving SGLT2 inhibitors served as the control group.
• The primary outcome was the time to ADT failure, defined as either biochemical progression or next-generation hormonal agent initiation. Secondary outcomes included time to next-generation hormonal agent failure, disease‑specific survival, and overall survival.
• The median follow-up duration was 66 months. SGLT2 inhibitors primarily included dapagliflozin and empagliflozin; a sensitivity analysis of metformin monotherapy was conducted as well.
• Overall, 6252 patients (44.0%) experienced ADT failure; the median time to ADT failure was 55 months. Among the 3358 patients who received next-generation hormonal agents, 1932 (57.5%) experienced treatment failure.

TAKEAWAY:

• The intention-to-treat analysis revealed that SGLT2 inhibitor use was associated with a 37% lower risk for ADT failure (hazard ratio [HR], 0.63; P = .03), resulting in an 11.1% decrease in the 10‑year cumulative event rate.
• Similarly, SGLT2 inhibitor use was associated with a 56% lower risk for next-generation hormonal agent failure (HR, 0.44; P = .04), resulting in an 8.4% decrease in the 10‑year cumulative event rate.
• Looking at survival outcomes, although estimates favored SGLT2 inhibitor use for disease‑specific survival (HR, 0.60; P = .37) and overall survival (HR, 0.70; P = .17), the associations were not statistically significant.
• In a subgroup analysis, metformin monotherapy was not associated with disease progression but was linked to improved overall survival (HR, 0.59; P = .002). No major differences in clinical outcomes were observed between dapagliflozin and empagliflozin.

IN PRACTICE:

In this study, “the use of SGLT2 inhibitors among patients with prostate cancer was associated with delayed hormone therapy failure,” the authors of the study wrote. But “prospective trials are warranted to validate these observations and assess their potential clinical applicability.”

SOURCE:

The study, led by Ruofan Shi, MBBS, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong (HKU) in Hong Kong, China, was published online in JAMA Oncology.

LIMITATIONS:

The relatively small number of patients who experienced next-generation hormonal agent failure after propensity-score matching limited statistical power. The absence of Gleason score data in the database precluded adjustment for tumor grade.

DISCLOSURES:

The study received support from the Health and Medical Research Fund of Hong Kong, the Shenzhen-Hong Kong-Macau Science and Technology Program, the Research Impact Fund of the University Grants Committee of Hong Kong, and the Seed Fund for PI Research-Translational and Applied Research at HKU. The authors reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.