Abstract
INTRODUCTION: Humulin R U-500 (U-500R) utilization has increased in the past few years, raising concerns as U-500R is indicated only for patients requiring > 200 units of insulin. Thus, evidence of dispensed total daily dose (dTDD) > 200 units of prior U-100 insulin based on pharmacy claims is increasingly used as a criterion to determine appropriate switching to U-500R by payers. The study compared the treatment patterns and outcomes before and after U-500R initiation among patients who were identified with ≤ 200 units/day U-100 insulin fill in order to understand the appropriateness of switching. METHODS: Patients with type 2 diabetes who initiated U-500R (index date = first fill) with ≤ 200 units/day pre-index dTDD and > 200 units/day post-index dTDD were identified in a Veterans Health Administration dataset between 1 January 2014 and 30 June 2017. Descriptive analysis was conducted on treatment patterns (dTDD, insulin dosage [units/kg], adherence, number of prescription fills) and clinical outcomes (HbA1c, symptomatic hypoglycemic events). Associations between U-500R exposure and outcomes were evaluated using mixed-effects models. Subgroups of U-500R syringe and KwikPen users were analyzed separately. RESULTS: Among 1191 U-500R initiators identified in the study the mean dTDD increased from the pre- to post-index periods (147.2 vs 346.3; p < 0.0001). The mean HbA1c decreased from pre- to post-initiation (9.6% vs 8.6%; p < 0.0001), and symptomatic hypoglycemia events per patient per year increased (2.0 vs 3.3, p < 0.0001). Mixed-effects models confirmed the significance of the changes (p < 0.0001). Device subgroups followed similar trends. CONCLUSIONS: U-500R initiation was associated with large dTDD increases, improved glycemic control, and modest increases in hypoglycemia events, suggesting U-500R initiation may have corrected previous treatment compliance issues. Imposing dTDDs > 200 units before switching to U-500R criterion could hurt the opportunities for patients who need a simplified regimen for better outcomes.