Can Diabetes Drugs Overcome Resistance in Prostate Cancer? The Effect of SGLT2 Inhibitors
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SGLT2 inhibitors (Jardiance, Forxiga, etc.), which transformed diabetes treatment, were found to increase hormone therapy (ADT) efficacy by 37% in prostate cancer. Published on January 8, 2026, in JAMA Oncology, this study provides strong evidence for drug repurposing in oncology.
Why Does It Matter?
The cornerstone of prostate cancer treatment is suppressing male hormones through androgen deprivation therapy (ADT). Unfortunately, tumor cells eventually develop resistance and disease progresses to the castration-resistant stage.
Options to overcome or delay this resistance are limited. The involvement of diabetes drugs, SGLT2 inhibitors , is therefore exciting. They may do more than lower blood glucose: disrupting tumor energy metabolism could starve cancer cells. Data from more than 14,000 patients turn this theory into a strong clinical finding.
Study Details: 14,223 Patients Examined
University of Hong Kong researchers performed a large target trial emulation using electronic health records from 1993-2025. It included men diagnosed with prostate cancer receiving hormone therapy (ADT): 14,223 male patients (median age 74).
- Comparison: Patients using SGLT2 inhibitors during hormone therapy were compared with nonusers.
- Focus: Time to "ADT failure," defined by rising PSA or the need to switch to next-generation drugs.
Striking Results: Resistance Is Delayed!
The data showed significantly slower disease progression among users:
Detailed Analyses
- Less Resistance to Next-Generation Drugs: Beyond first-line treatment, the risk of resistance to stronger drugs used after progression, such as abiraterone and enzalutamide, fell by 56% (HR: 0.44; P = .04).
- The 10-Year Difference: The cumulative failure rate at 10 years was 11.1% lower among users. Clinically, this means patients remaining stable for years without additional treatment.
- The Metformin Difference: Our old friend metformin was also examined. Unlike SGLT2 inhibitors, it did not halt progression as measured by PSA increase, but it improved overall survival (OS) (HR: 0.59). This suggests the drugs work through different mechanisms.
Note: Although OS data showed a trend favoring SGLT2 inhibitors, it was not statistically significant. Disease-control success, however, was indisputable.
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Metabolism and Cancer: A New Front
Dear colleagues, this study again reminds us to manage the patient's entire metabolism rather than only the cancer cell.
Clinical Implications:
New or worsening diabetes is a common side effect in our ADT patients. This study suggests prioritizing SGLT2 inhibitors (dapagliflozin, empagliflozin) when choosing diabetes medication in prostate cancer. They regulate glucose, protect the heart, and apparently overcome tumor resistance.
Although these data are retrospective, the biological rationale—tumor glucose dependence—is strong. It would not be surprising if these drugs became a standard adjuvant component of prostate cancer treatment.