Published online Feb 15, 2018. doi: 10.4239/wjd.v9.i2.53
Peer-review started: January 8, 2018
First decision: February 9, 2018
Revised: February 13, 2018
Accepted: February 14, 2018
Article in press: February 14, 2018
Published online: February 15, 2018
Processing time: 57 Days and 14.6 Hours
Several case reports and series have described dramatic acute hypoglycemic effects for the immunosuppressive agents collectively called tumor necrosis factor inhibitors (TNFi’s). In addition, studies have shown various cardioprotective and metabolic effects for conventional anti-rheumatic therapies; however, few studies have examined acute blood glucose effects for these agents in large population studies.
A better estimate of frequency and scale hypoglycemia associated with the initiation of medicines for users of TNFi and other anti-inflammatory medications may give insight into the role of cytokines and the inflammatory cascade in glucose tolerance as well as better estimate risks and benefits for these medications to the clinician.
We wished to determine whether initiation of tumor necrosis factor inhibitors in rheumatoid arthritis patients leads to reductions in blood glucose as measured by random blood glucose or glycosylated hemoglobin A1c. Simultaneously, we wished to investigate for similar effects in conventional antirheumatic drugs, given the established lipid homeostasis and cardioprotective effects for these agents.
An observational registry linking pharmacy, clinical laboratory, and other data was utilized to retrospectively identify the time of prescription of the agents in question. This registry and linked data was used to retrospectively identify glucose measures proximate to these medication start events, so that changes in blood glucose surrounding the medication start could be inferred.
Cohort-level glucose effects were not identified in this registry surrounding the start of tumor-necrosis factor inhibitors, although glucose-lowering changes were identified surrounding the initiation of the conventional antirheumatic treatments sulfasalazine and hydroxychloroquine. Hyperglycemic changes surrounding prednisone were identified, lending further internal validity to these results.
This study adds to the literature supporting the potentially beneficial metabolic effects of conventional anti-rheumatic therapies sulfasalazine and hydroxychloroquine beyond their general anti-inflammatory effects. These data also lend reassurance against large-scale prevalence for previously reported adverse hypoglycemic effects for tumor-necrosis factor inhibitors. The results point to the need for additional, similar studies in other populations, particularly those with spondyloarthritis syndromes such as psoriatic arthritis.
This study, while a null result regarding tumor necrosis factor-inhibitor-associated hypoglycemic effects, points to the need for additional clarification on the physiology and causes for hypoglycemic events with these medications. We suggest the need for similar studies in psoriasis and psoriatic arthritis patients, as well as the potential utility of a case-control approach for the future study of dramatic hypoglycemic effects and events with immunosuppressive medications.