A retrospective study recently published in the journal “Arthritis Care & Research” reports that tumor necrosis factor (TNF) inhibitors could help prevent diabetes in patients with rheumatoid arthritis (RA), who commonly take TNF inhibitors to help in preventing joint disease.
The study, which was funded by Amgen/Wyeth, found that adults with RA who were treated with TNF inhibitors were much less likely to develop diabetes over the three to four year period following treatment over individuals who were not treated with TNF inhibitors.
“In RA patients, use of TNF inhibitors is associated with 51% reduction in risk of developing diabetes,” said Androniki Bili M.D., M.P.H., of the Center for Health Research at the Geisinger Medical Center in Danville, Pennsylvania. Dr. Bili served as co-author on the study. He did note that retrospective studies such as this one can only determine associations between conditions and cannot positively identify causation.
The study included data from 1881 adults who had been diagnosed with RA between January 1, 2001 and December 21, 2009. Patients who already had diabetes, of which there were 294, were excluded from the study. The researchers utilized proportional hazard regression models to adjust their findings to account for a variety of confounding factors, including age, race, sex, body mass index, rheumatoid factor, and anticyclic citrullinated peptide antibodies.
After exclusions, data from 1587 patients remained. Of the cohort, 522 were users of TNF inhibitors; 91 patients had developed diabetes throughout the course of the study, among them 16 users of TNF inhibitors and 75 non-users. Diabetes incidence rates stood at 8.6 and 17.2 per 1000 person-years for TNF inhibitor users and non-users, respectively. After adjusting for covariates, researchers were left with a hazard ratio of 0.49 for users of TNF inhibitors as opposed to non-users.
“RA is a systemic inflammatory disease with major cause of death being cardiovascular disease due to accelerated atherosclerosis,” explained Dr. Bili. “Diabetes and metabolic syndrome are major risk factors for cardiovascular disease. Therefore, medications that treat both the joints and the cardiometabolic comorbidities of RA are highly desirable. Although not an official guideline, I believe that patients with RA and metabolic syndrome, insulin resistance, or [body mass index greater than] 25 kg/m2 (all risk factors for diabetes) might benefit from earlier initiation of a TNF-a inhibitor in an attempt to control the cardiometabolic comorbidities along with the joint disease.”
According to Dr. Bili, his team’s findings support the hypothesis that TNF-a plays an important role in pathogenesis of insulin resistance—or the onset of insulin resistance, which often precedes Type 2 diabetes.
The study was reviewed by Daniel Solomon, M.D., M.P.H., who had previously observed a similar decrease in diabetes risk for patients with RA who were treated with TNF inhibitors.
“The authors conducted an interesting set of analyses and came to similar conclusions as we did in a recent paper published in JAMA,” said Dr. Solomon, referring to his own similar findings. “Their data set includes some potentially important variables that our analyses could not include. Thus, this paper adds to the literature.”
However, Dr. Solomon warned that even though the studies demonstrated similar results, they did not warrant a conclusion that TNF inhibitors directly cause the reduced incidence of diabetes.
“While there is a biologic basis that may link the use of TNF inhibitors to a reduced risk of incident diabetes, 2 epidemiologic studies do not prove causation. It would be premature for doctors to incorporate these findings into their management of systemic rheumatic diseases. However, studies suggesting a link between TNF inhibitors and diabetes risk reduction speak to the inflammatory basis of diabetes and insulin resistance. This study should encourage other investigators considering immunosuppressive treatments for diabetes prevention and treatment,” said Dr. Solomon.