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2025 David H. Koch Charitable Foundation – PCF Young Investigator Award

Assessing the Impact of GLP-1 Receptor Agonists and SGLT2 Inhibitors on Advanced Prostate Cancer Risk and Outcomes

Kevin Kensler, ScD
Weill Cornell Medicine

Mentors: David Nanus; Laura Pinheiro; Lorelei Mucci

Description:

  • Obesity and diabetes are common comorbidities in men with prostate cancer, worsening prognosis. GLP-1 receptor agonists (GLP-1 RAs) and SGLT2 inhibitors (SGLT2is) have transformed diabetes and weight management, offering benefits beyond glycemic control, including cardiovascular and metabolic health. Their rapid adoption in prostate cancer patients necessitates research into their effects on advanced prostate cancer risk, outcomes, and interactions with therapies.  Androgen deprivation therapy (ADT) is a cornerstone treatment for advanced prostate cancer but is associated with substantial metabolic and cardiovascular toxicity, including increased fat mass, loss of lean muscle, insulin resistance, heightened cardiovascular disease risk, and deficits in quality of life.
  • Dr. Kevin Kensler’s project will use existing large real-world clinical datasets to assess whether GLP-1 RAs/SGLT2is impact the risk of aggressive prostate cancer in men without a history of prostate cancer, and to evaluate if concurrent use of these medications in patients with prostate cancer at ADT initiation affects treatment efficacy or toxicities. 
  • A pilot clinical trial will also be conducted to examine the impact of GLP-1 RAs on weight, body composition, and metabolic biomarkers in prostate cancer patients initiating ADT.
  • If successful, these studies will provide critical initial insights into whether the new diabetes and weight loss drugs GLP-1 RAs/SGLT2is can modulate prostate cancer risk and progression, improve the efficacy of ADT, mitigate metabolic toxicities, and improve quality of life for patients living with prostate cancer. The findings will inform larger-scale studies and future clinical trials evaluating these agents as supportive care strategies in prostate cancer.

What this means to patients: Obesity and diabetes are associated with worse outcomes in patients with prostate cancer. Dr. Kensler’s project will investigate whether new therapies for diabetes and weight management, GLP-1 receptor agonists and SGLT2 inhibitors, can improve prostate cancer outcomes, particularly in patients undergoing treatment with ADT, which increase risk for metabolic and cardiovascular toxicities. These studies could lead to new strategies to enhance broader health and quality of life in patients with prostate cancer, and potentially ultimately reduce patient mortality.