INSIGHTFUL observational evidence suggests that sodium–glucose cotransporter 2 (SGLT2) inhibitors, commonly prescribed for type 2 diabetes, may delay disease progression in men with prostate cancer receiving hormone therapy.
In a large population-based cohort study, use of SGLT2 inhibitors was associated with significantly lower risks of androgen deprivation therapy (ADT) failure and next-generation hormonal agent failure among patients undergoing hormonal treatment for prostate cancer.
The study used a sequential target trial emulation design and analysed territory-wide electronic health records from the Hong Kong Hospital Authority, covering a population of approximately 7.5 million. A total of 14,223 men with prostate cancer who initiated ADT were included, with a median age of 74 years and a median follow-up of 66 months.
SGLT2 Inhibitors vs Other Antidiabetic Therapies
SGLT2 inhibitor exposure, primarily dapagliflozin and empagliflozin, was defined as treatment initiated during hormone therapy and continued for at least one month. In intention-to-treat analyses, SGLT2 inhibitor use was associated with a 37% lower risk of ADT failure (hazard ratio [HR] 0.63, 95% CI 0.41–0.95; p=0.03). The risk of next-generation hormonal agent failure was also significantly reduced, with an HR of 0.44 (95% CI 0.20–0.97; p=0.04).
Sensitivity analyses across different comparator subgroups confirmed the robustness of these findings. Notably, no statistically significant differences in outcomes were observed between dapagliflozin and empagliflozin, suggesting a potential class effect.
The authors also examined other antidiabetic therapies. Metformin monotherapy was not associated with reduced disease progression but was linked to improved overall survival (HR 0.59, 95% CI 0.42–0.83; p=0.002), aligning with previous observational data on metformin’s possible survival benefits in cancer.
Implications for Clinical Practice and Patient Care
While the biological mechanisms remain speculative, preclinical studies have suggested that SGLT2 inhibitors may exert antitumour effects through modulation of tumour metabolism, insulin signalling, and systemic inflammation.
The investigators emphasise that, as an observational study, causality cannot be established. Residual confounding and treatment selection bias may persist despite the robust target trial emulation design. Nevertheless, the findings raise the possibility that SGLT2 inhibitors could serve as adjuncts to hormonal therapy in prostate cancer.
Prospective clinical trials will be needed to determine whether SGLT2 inhibitors can safely and effectively improve oncological outcomes in this population beyond their established glucose-lowering benefits.
Reference
Shi R et al. Sodium-Glucose Cotransporter 2 Inhibitors for Patients With Prostate Cancer Undergoing Hormone Therapy. JAMA Oncol. 2026; doi:10.1001/jamaoncol.2025.5869
