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
To determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study.
Patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were selected who, during follow-up, initiated treatment with tumor necrosis factor inhibitors (TNFi’s, including etanercept, adalimumab, infliximab, golimumab, or certolizumab), prednisone, or conventional disease-modifying anti-rheumatic drugs (DMARDs), and for whom proximate random blood glucose (RBG) measurements were available within a window 2-wk prior to, and 6 mo following, medication initiation. Similar data were obtained for patients with proximate values available for glycosylated hemoglobin A1C values within a window 2 mo preceding, and 12 mo following, medication initiation. RBG and A1C measurements were compared before and after initiation events using paired t-tests, and multivariate regression analysis was performed including established comorbidities and demographics.
Two thousands one hundred and eleven patients contributed at least one proximate measurement surrounding the initiation of any examined medication. A significant decrease in RBG was noted surrounding 653 individual hydroxychloroquine-initiation events (-3.68 mg/dL, P = 0.04), while an increase was noted for RBG surrounding 665 prednisone-initiation events (+5.85 mg/dL, P < 0.01). A statistically significant decrease in A1C was noted for sulfasalazine initiation, as measured by 49 individual initiation events (-0.70%, P < 0.01). Multivariate regression analyses, using methotrexate as the referent, suggest sulfasalazine (β = -0.58, P = 0.01) and hydroxychloroquine (β = -5.78, P = 0.01) use as predictors of lower post-medication-initiation RBG and A1C values, respectively. Analysis by drug class suggested prednisone (or glucocorticoids) as predictive of higher medication-initiation event RBG among all start events as compared to DMARDs, while this analysis did not show any drug class-level effect for TNFi. A diagnosis of congestive heart failure (β = 4.69, P = 0.03) was predictive for higher post-initiation RBG values among all medication-initiation events.
No statistically significant hypoglycemic effects surrounding TNFi initiation were observed in this large cohort. Sulfasalazine and hydroxychloroquine may have epidemiologically significant acute hypoglycemic effects.
Core tip: Clinicians should be cognizant of the potential for rare hypoglycemic effects of the conventional disease-modifying anti-rheumatic drugs hydroxychloroquine and sulfasalazine, in addition to the well-known hyperglycemic effects of glucocorticoids. Although case reports describe dramatic sporadic hypoglycemic events with the initiation of tumor necrosis factor inhibitors, these effects were not confirmed in our large retrospective study.