Healthcare Costs and Adherence Associated With Human Regular U-500 Versus High-Dose U-100 Insulin in Patients With Diabetes

Elizabeth L. Eby, MPH; Anthony J. Zagar, MS; Ping Wang, PhD; Bradley H. Curtis, PhD; Jin Xie, MS; Diane C. Haldane, MS; Iskandar Idris, MD; Anne L. Peters, MD; Robert C. Hood, MD; Jeffrey A. Jackson, MD


Endocr Pract. 2014;20(7):663-670. 

In This Article

Abstract and Introduction


Objective: Describe the characteristics, costs, and adherence of patients receiving human regular U-500 insulin (U-500R) compared with those of patients receiving high-dose (≥150 units/day) U-100 insulin.

Methods: Data from Truven Health MarketScan Research Databases, July 1, 2008, through December 31, 2010, were used. The U-100 cohort received ≥150 units/day of U-100 insulin for ≥31 days during the first 60 days after the index date. The U-500R cohort received ≥2 prescriptions of U-500R after the index date. Analyses were performed on propensity-matched cohorts. The changes in annualized costs were compared between the 2 cohorts using paired t tests. Adherence was assessed by the proportion of days covered (PDC) and compared using a 2-sample t test. Glycemic efficacy data were not available in this database.

Results: There were 1,044 U-500R–treated patients (19.1% with type 1 diabetes [T1D]) and 11,520 U-100– treated patients (23.8% with T1D) identified, from which 1,039 matched pairs were obtained. The mean decrease of $1,290 in annual pharmacy costs for the U-500R cohort was significantly different from the mean increase of $2,586 for the U-100 cohort (P<.001; 95% confidence interval, –$4,345 to –$3,422). More U-500R patients experienced hypoglycemia (17.3% vs. 11.8%; P<.001), but the hypoglycemia rate per person and related costs were not significantly different between cohorts. Finally, the mean 12-month PDC was 65.0% for U-500R versus 47.6% for U-100 patients (P<.0001).

Conclusion: Compared with treatment with ≥150 units/day of U-100 insulin, treatment with U-500R was associated with decreases in pharmacy costs, a higher percentage of patients experiencing hypoglycemia, and greater treatment adherence.


The rising global incidence of diabetes and obesity creates challenges for clinicians in managing the increasing numbers of patients who require high doses of insulin to achieve glycemic goals.[1–6] Severe insulin resistance (insulin requirements of >2 units/kg/day or >200 units/day [4,5]) occurs in patients with type 1 diabetes (T1D) and patients with type 2 diabetes (T2D) who inject large volumes of prandial/basal insulins that may call for 8 or more separate injections per day. Despite increasing use of human regular U-500 insulin (U-500R; 500 U/mL: Humulin® R U-500; Eli Lilly and Company, Indianapolis, IN),[7] limited data exist regarding the characteristics of patients requiring high-dose insulin and their clinical and economic outcomes. The objectives of this study were to describe the characteristics, healthcare costs (including those of hypoglycemic events), and adherence of U.S. patients receiving U-500R compared with patients receiving high doses (≥150 units/day) of U-100 insulins for treatment of diabetes.