OBJECTIVES: Diabetes is a chronic and progressive disease that for many patients requires initiation and intensification of insulin in order to sustain glycemic control and thereby lower risk of long-term complications. Insulin intensification, however, can have some negative consequences for patients in the form of increased risk of hypoglycemic events. This analysis asks the question to what extent the administration vehicle, prefilled pen versus vial and syringe, has an impact on the risk of hypoglycemic events. METHODS: This is a retrospective database analysis comparing the incidence of hypoglycemia-related health care utilization between patients that were previously naïve to short-acting insulin initiating the short-acting insulin analogue, insulin aspart (IAsp), in either a vial or in a prefilled disposable pen (FlexPen®). Data were derived from healthcare claims for individuals with employer-sponsored primary or Medicare supplemental insurance between 2004 and 2007. The analysis was conducted using logistic regression technique controlling for age, gender, diabetes type, pre-index hypoglycemic incidence, pre-index diabetes treatments and daily consumption of IAsp. Evaluation period was 12 months. RESULTS: The cohorts consisted of 5523 vial patients and 6065 FlexPen® patients. Mean age of the two cohorts were 53.6 and 56.2 years (p<0.0001) in vial and FlexPen® groups, respectively. Fifty-one percent and 54% (p=0.05) of the populations were males. Generally, a larger proportion the FlexPen® versus the vial cohort were already on an insulin regimen (basal or premix). Mean number of annual hypoglycemia-related health care utilization incidence in the period following initiation of IAsp were 1.27 and 0.87 (p<0.0001) for vials and FlexPen®, respectively. After multivariate adjustment the odds ratio of hypoglycemic incidence with vials versus FlexPen® was 1.36 (CI: 1.20-1.54). CONCLUSIONS: After controlling for potential confounders the incidence of hypoglycemia-related health care utilization were 36% higher when initiating IAsp in a vial compared to initiation with FlexPen®.