TNF Inhibitors Linked to Reduced Risk for Diabetes

October 13, 2011 — Tumor necrosis factor (TNF) inhibitors might provide an additional benefit to patients with rheumatoid arthritis (RA) that is beyond their effect on joint disease: some protection against developing diabetes.

A retrospective study funded by Amgen/Wyeth, published online October 5 in Arthritis Care & Research, finds that adults with RA treated with TNF inhibitors were significantly less likely to develop diabetes during the next 3 to 4 years than those never treated with these drugs.

Coauthor Androniki Bili, MD, MPH, from the Center for Health Research at Geisinger Medical Center in Danville, Pennsylvania, told Medscape Medical News: ”In RA patients, use of TNF inhibitors is associated with 51% reduction in risk of developing diabetes.” Dr. Bili warned that retrospective observational studies can only show association and not causation, however.

The study included 1881 adults diagnosed with RA between January 1, 2001, and December 31, 2009. Those with diabetes at baseline were excluded (n=294), and proportional hazard regression models were used to adjust for age, sex, race, body mass index, rheumatoid factor, anticyclic citrullinated peptide antibodies, erythrocyte sedimentation rate, and use of nonsteroidal anti-inflammatory drugs, glucocorticoids, hydroxychloroquine, and methotrexate.

Of the 1587 patients included in the analysis, 522 were TNF-inhibitor users. Ninety-one patients developed diabetes, of whom 16 had used TNF inhibitors and 75 had not, for diabetes incidence rates of 8.6 and 17.2 per 1000 person-years, respectively (P = .048). The hazard ratio after adjusting for the covariates was 0.49 for TNF-inhibitor users vs never-users (95% confidence interval, 0.24 – 0.99; P = .049).

Dr. Bili said, ”RA is a systemic inflammatory disease with major cause of death being cardiovascular disease due to accelerated atherosclerosis. 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-α inhibitor in an attempt to control the cardiometabolic comorbidities along with the joint disease.”

Dr. Bili noted that his group’s data reinforce the notion that TNF-α plays a central role in the pathogenesis of insulin resistance, which is a major risk factor for diabetes.

Daniel Solomon, MD, MPH, who observed a similar decreased diabetes risk in patients with RA or psoriasis treated with TNF inhibitors, reviewed the study for Medscape Medical News.

Dr. Solomon said, ”The authors conducted an interesting set of analyses and came to similar conclusions as we did in a recent paper published in JAMA. Their data set includes some potentially important variables that our analyses could not include. Thus, this paper adds to the literature.”

Dr. Solomon is chief, Section of Clinical Sciences, Division of Rheumatology and Division of Pharmacoepidemiology, Brigham and Women’s Hospital, Boston, Massachusetts.

Dr. Solomon was more cautious than Dr. Bili with regard to the clinical implications, however.

”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,” Dr. Solomon said.

Dr. Bili and 2 other authors received salary support from Amgen/Wyeth for work on this manuscript; one of these authors has also received consultancy fees and other financial support from UCB and Centocor. Dr. Solomon has received research grant support from Abbott and from Amgen; he has also directed an educational course supported by Bristol-Myers Squibb and served in an unpaid role on 2 Pfizer-sponsored trials.

Arthritis Care Res. Published online October 5, 2011. Abstract. From Medscape/ADA

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Publicerad: |2011-10-16|