In a cohort of individuals with type 2 diabetes using the drug sulfasalazine, HbA1c lowering is associated with haematological changes

Objectives: Several small studies indicate the sulphonamide component of the drug sulfasalazine lowers HbA _1c. We investigated reduction of HbA _1c following incident prescription of sulfasalazine and related aminosalicylates, lacking the sulphonamide group, in an observational cohort. Research Design and Methods: Individuals in the Scottish Care Information Diabetes Collaboration (SCI-Diabetes) with type 2 diabetes and incident prescription for an aminosalicylate drug (sulfasalazine, mesalazine, olsalazine or balsalazide) were identified. Baseline and 6-month HbA _1c were required for eligibility, to calculate HbA _1c response. To investigate association with haemolysis, change in components of full blood count was assessed. Paired t-tests compared difference in baseline and treatment HbA _1c measures and other clinical variables. Results: In all, 113 individuals treated with sulfasalazine and 103 with mesalazine (lacking the sulphonamide group) were eligible, with no eligible individuals treated with olsalazine or balsalazide. Baseline characteristics were similar. Mean (SD) HbA _1c reduction at 6 months was −9 ± 16 mmol/mol (−0.9 ± 1.4%) (p < 0.0001) in those taking sulfasalazine with no reduction in those taking mesalazine (2 ± 16 mmol/mol (0.2 ± 1.4%). Sulfasalazine but not mesalazine was associated with a mean (SD) increase in mean cell volume of 3.7 ± 5.6 fl (p < 0.0001) and decrease in red cell count of −0.2 ± 0.4 × 10 ⁻¹²/L (p < 0.0001). Conclusions: In this observational, population-based study, sulfasalazine initiation was associated with a 6-month reduction in HbA _1c. This correlated with haematological changes suggesting haemolytic effects of sulfasalazine. Haemolysis is proposed to contribute to HbA _1c lowering through the sulphonamide pharmacophore. This suggests that HbA _1c is not a reliable measure of glycaemia in individuals prescribed sulfasalazine.