Androgen deprivation therapy raises new-onset diabetes risk 43% in 1 year

Anaheim, CA-Initiating androgen deprivation therapy (ADT) in men with prostate cancer significantly increases the risk of incident diabetes, and that effect occurs within a relatively short time frame, according to research presented at the AUA annual meeting here.

Researchers from pharmaceutical maker Amgen used a retrospective insurance claims database that includes more than 5.3 million lives. They searched the database for men who were diagnosed with prostate cancer between May 2000 and March 2005 and who were in the database with continuous insurance coverage for at least 6 months prior to that index date with no diagnosis of diabetes, for at least 12 months after prostate cancer diagnosis, and-for men who received ADT-for at least 12 months after initiating that treatment.

A total of 8,481 men fulfilled those criteria, including 1,231 men who received ADT (LHRH agonist, LHRH antagonist, anti-androgen, or other androgen-suppressing agent) and 7,250 men who were not treated with ADT or orchiectomy.

"The adverse physiologic effects of ADT have been well described, including rapid loss of bone and lean body mass and gains in fat mass, and there is accumulating evidence showing ADT is associated with features defining the metabolic syndrome, including dyslipidemia, hypertension, and insulin resistance," said Richard Markus, MD, PhD, director of global development, Oncology Supportive Care, Amgen, Thousand Oaks, CA, who worked on the study with Beth Barber, PhD, and collaborators. "Our interest in performing this study was to go a step forward in examining the risks of ADT to see if it was associated with onset of overt clinical diabetes.

"Our analyses have some limitations inherent in using a single insurance claims database, and we lacked information on the patient's diet and prostate cancer stage and Gleason score. The results, however, reinforce that although ADT is a mainstay of treatment for men diagnosed with metastatic or locally advanced prostate cancer, physicians must weigh its serious side effects alongside its potential benefits."

Other comparisons between the ADT and no-ADT groups showed that men who received ADT were significantly older (p<.0001) and were also in poorer health, as defined by the Charlson Comorbidity Index. A significantly higher proportion (p=.0091) of the ADT-treated men also had a prior diagnosis of hypertension. No baseline significant differences were noted between the ADT and no-ADT cohorts in other variables examined, which included region of residence, type of insurance coverage, or proportion of patients with obesity, congestive heart failure, or cardiovascular disease.

In the multivariate analysis to identify independent predictors of diabetes, onset, age, hypertension, CHF, and geographic region of residence were statistically significant.

"The risk associated with ADT was higher than all of those variables, with the exception of CHF," Dr. Markus told Urology Times.

The highest proportion of men in this claims-based analysis resided in the South. That population was used as the reference group in the multivariate analysis to assess the impact of regional variation on incident diabetes.

"Although our study did not include information on diet, which is an important potential confounder, we expect differences in that variable may be partially controlled for by the geographic categorization. There is no rationale for why, prior to initiation of ADT, there would be a difference in diet between men receiving ADT and those [who are] not," Dr. Markus said.

The study was supported by Amgen and conducted by HealthMetrics Outcomes Research, Groton, CT.