Also, they said, the criteria used to perform laser therapy were not defined in the study protocol, and therefore they probably varied among the study centers. The number of patients in the retinal substudy was small, making it impossible to draw definitive conclusions based on 5 years of follow-up. Finally, there is no clear explanation of how fenofibrate affects diabetic retinopathy.
Possible mechanisms include documented anti-inflammatory effects of fenofibrate, the drug's inhibitory effect on endothelial cell migration, and the drug's reduction of apoptosis in retinal endothelial cells, said Jean-Charles Fruchart, Ph.D., head of the department of atherosclerosis at the Pasteur Institute of Lille, France, during the press briefing. The retinopathy effect did not appear to be mediated by an effect on blood pressure or glycemic control, because fenofibrate had little or no effect on these.
Additional evidence of beneficial effects of fenofibrate on microvascular disease in patients with diabetes comes from observations of the drug's effect on renal function and neuropathy. Progression of albuminuria occurred in 11% of placebo patients and 9% of those on fenofibrate, a 15% relative risk reduction, Dr. Keech said. And regression of albuminuria occurred in 9% of patients treated with fenofibrate and 8% of placebo patients, a 14% relative increase.
In addition, amputations were lowered from a 1.5% rate with placebo to a 0.9% rate with fenofibrate, a relative risk reduction of 38% that was statistically significant. The amputation rate was reported by Dr. Keech and his associates in a separate report during the American Heart Association's meeting.