Anti-Diabetic Drug Could Offer New Treatment for Prostate Cancer

An anti-diabetic peroxisome proliferator-activated receptor (PPARy) agonist drug, pioglitazone (Actos; Takeda Pharmaceuticals), used to treat type 2 diabetes (T2D) could also be effective in slowing the progression of prostate cancer (PCa), according to research published by investigators in the journal Molecular Cancer.^1,2

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PCa is marked as the second most prevalent cancer in men, which is commonly found early and often grows slowly. If found in an earlier stage, individuals can receive various treatment options, including surgery, radiation therapy, or monitoring its growth. However, if the cancer grows beyond the prostate or spreads, while there are many treatment options, curing it becomes more difficult, according to Mayo Clinic.³

On top of being at risk of developing PCa, men are also more prone to T2D compared to women. The heterogeneous, chronic disease is the most common metabolic disorder diagnosed in the world, caused by insulin resistance. The simultaneous occurrence of PCa and T2D becomes more common with increasing age and obesity, creating considerable challenges in both epidemiology and treatment. Despite this, the exact connection between PCa and T2D is still unclear, as current research offers contradictory findings. Previous studies indicate that PCa patients with T2D may be protected from PCa disease progression, but mortality rates are typically higher when T2D is not effectively treated.¹

Researchers conducted a study to assess common and specific molecular pathways targeted by the PPAR agonists bezafibrate (Bezalip; Cenexi SAS), tesaglitazar (Galida; AstraZeneca), and pioglitazone. A total of 69 PCa patients with T2D were included, along with a combination of studies that included cells and mice.^1.2

The results indicated that high expression of PPARy is associated with worse survival in advanced PCa, which is supported by previous studies. However, the study authors noted that the findings also demonstrate that pioglitazone significantly reduced the proliferation of PCa cells in laboratory settings and the growth of metastatic tumors in animal models. This effect was linked to a decrease in PPARy protein and a shift towards an epithelial cell type. Conversely, other studies reported that overexpression of PPARy can promote tumor growth and metastasis, while its reduction or treatment with certain PPARy agonists can inhibit PCa growth and increase epithelial markers.^1,2

"This is a significant discovery. For the first time, we have clinical observations showing that prostate cancer patients with diabetes who received drugs targeting the protein remained relapse-free during the period we followed them," Lukas Kenner, visiting professor at Umeå University and one of the study's lead authors, said in a news release.¹

Further results revealed that pioglitazone altered the protein profile and metabolism of PCa cells, reducing mitochondrial adenosine triphosphate (ATP) production and affecting key signaling pathways. The study authors noted that the results highlight that PCa undergoes significant metabolic shifts during its progression, which influences its response to therapy. The findings suggest that pioglitazone aims to counteract tumor-promoting effects by changing the cellular metabolism and could also reduce inflammation.^1,2

However, beyond PPARy agonists, other antidiabetic drugs like metformin, DPP4 inhibitors, and SGLT-2 inhibitors have shown promise in reducing the incidence of progression of various cancers, including PCa.¹

"The findings are very promising," Kenner concluded in a news release. "But further clinical studies are needed to both confirm the results and to investigate whether the treatment can also be used in patients with prostate cancer who do not have diabetes."¹

REFERENCES

1. Schauer, A., Stangl, D., Kureli, J., Hackl, H., Morak, M., Schossmann, P., Kenner, L. May 5, 2025. Accessed May 20, 2025. The anti-diabetic PPARγ agonist Pioglitazone inhibits cell proliferation and induces metabolic reprogramming in prostate cancer. Molecular Cancer, 24(1), 134. https://doi.org/10.1186/s12943-025-02320-y

2. Diabetes drug gives hope for new treatment for prostate cancer. EuerkAlert!. News release. May 20, 2025. Accessed May 20, 2025. https://www.eurekalert.org/news-releases/1084203

3. Prostate Cancer. Mayo Clinic. News release. February 20, 2025. https://www.mayoclinic.org/diseases-conditions/prostate-cancer/symptoms-causes/syc-20353087