Early Metabolic Abnormalities Common With ADT and ARPI Therapy in prostate cancer patients: Study

A new study published in the Journal of the American Medical Association found that metabolic abnormalities were frequently documented soon after starting androgen deprivation therapy (ADT) combined with androgen receptor pathway inhibitors (ARPIs) in men with advanced prostate cancer. The findings highlight the importance of systematic early monitoring of glucose, lipids, weight, blood pressure, and other cardiometabolic risk factors, along with cancer outcomes. Multidisciplinary care and scalable interventions may help identify and manage metabolic dysfunction early.

This retrospective study analyzed data from 16,924 men with prostate cancer who had no evidence of metabolic syndrome or its individual components before beginning combined ADT-ARPI therapy. Using the Epic Cosmos national electronic health record database, researchers tracked patients treated between January 2014 and September 2025, with up to 12 months of follow-up after therapy initiation.

This study observed that the cumulative incidence of metabolic syndrome rose steadily throughout the first year of treatment, reaching nearly 40% of patients. The findings indicate that metabolic complications can emerge much sooner than previously appreciated after the initiation of combination hormonal therapy. Men aged 70 to 79 years experienced the highest incidence of metabolic syndrome, with 51.7 events per 1,000 person-months. The study also found that metabolic outcomes differed across age groups, suggesting that older patients may require closer surveillance during treatment.

Among the individual metabolic abnormalities, hypertension was the most frequently documented condition, followed by other features associated with metabolic syndrome, including obesity, insulin resistance, and abnormal lipid levels. This study also reported differences in metabolic outcomes according to the type of ARPI prescribed. Enzalutamide was the most commonly used ARPI in the study cohort, although exploratory analyses suggested that metabolic risks may vary among different ARPI agents, including abiraterone acetate, apalutamide, and darolutamide.

The study population had a mean age of 73.1 years and included a diverse patient group, with non-Hispanic White individuals comprising 65.5% of participants, non-Hispanic Black individuals 21.0%, Hispanic individuals 5.4%, and Asian individuals 3.0%. Most patients received medical rather than surgical androgen deprivation therapy.

Metabolic syndrome is characterized by a combination of conditions that substantially increase the risk of cardiovascular disease and type 2 diabetes. While ADT has long been associated with adverse metabolic effects, evidence describing the timing and extent of these complications after adding modern ARPIs has been limited. Overall, the findings suggest that metabolic abnormalities are frequently documented soon after initiating concurrent ADT and ARPI therapy, highlighting the need for systematic metabolic assessment throughout prostate cancer care. 

Source:

Shaver, A. L., Zarrabi, K. K., Nikita, N., Sharma, S., Wen, K.-Y., & Lu-Yao, G. (2026). Metabolic dysfunction after initiation of androgen receptor pathway inhibitors in prostate cancer. JAMA Oncology. https://doi.org/10.1001/jamaoncol.2026.2790