The majority of patients initiating mealtime insulin had a 90-day gap in mealtime insulin claims (81%) during the year following their first mealtime insulin claim. According to Sikka and colleagues, patients filling claims following an allowable gap are still considered non-persistent . However, the presence of a 90-day gap is not a measure of complete discontinuation; 87% of patients with a 90-day gap had a mealtime insulin claim following the gap. Of the 3,843 patients with a 90-day claim gap, nearly half (46.2%) had a gap immediately following their index claim. Using a 90-day gap to define insulin persistence increases the likelihood of falsely classifying persistent patients as non-persistent. According to measure 2, which is more lenient and allows for sizeable gaps between the required number of insulin claims, less than half of patients (42%) were persistent at 12 months.
A significant number of patients who met the study inclusion and exclusion criteria (17%) were excluded because they only filled their index mealtime insulin claim. A single mealtime insulin claim may indicate a response to an acute hyperglycemic event and not represent a true intensification of diabetes management. Further investigation of these patients and their reasons for early discontinuation is warranted.
Several factors could be related to the findings regarding insulin type (analog versus human) and delivery (pen versus vial/syringe). Previous research has found that a dislike of injections is related to discontinuing insulin use , which might imply that insulin pens may have better persistence than vial/syringe due to the somewhat different nature of the injection. However, this study failed to find a statistically significant relationship between insulin pen use and persistence, similar to the findings of Pawaskar and colleague . This finding may be partly due to the availability of products and the study timeframe. At the same time, the greater dosing flexibility may have contributed to the consistent association between analog insulin and increased persistence. This current analysis could not, however, control for provider-related characteristics or preferences that may be related to insulin persistence and the use of human versus analog or pen versus vial/syringe insulin.
The finding that higher counts of concomitant diabetes medications were positively associated with insulin persistence is inconsistent with existing literature . This association could be due, in part, to the fact that the use of additional classes of OAD agents are a result of healthcare utilization and monitoring. It is also possible that collinearity between the count of OAD classes and diabetes complications is interfering with the multivariate models. This may explain the change in direction from the univariate to the multivariate results.
Caution should be used when interpreting the results of persistency to insulin therapy. There is no validated measure available to measure insulin adherence and persistence. The presence of a claim gap (measure 1) is a commonly used measure for persistency . The original formulation of measure 2 incorporated the current number of claims structure and a requirement of 0.10 mL index insulin per day, on average. Descriptive analyses of the average quantity of insulin per day did not provide a clear, clinically relevant cut-off that did not appear arbitrary. Descriptive analysis also indicated that the number of claims requirement, as opposed to the insulin quantity per day, largely determined persistence status. Both of these reasons support excluding insulin quantity per day from persistence determination.
By either measure, non-persistence indicates a significant break in a patient's use of mealtime insulin that is reflected both in time off of therapy and in average daily dose of insulin. Non-persistent patients had an average total daily insulin dose of 0.30 mL (non-persistent by measure 1) and 0.27 mL (non-persistent by measure 2), which included average daily mealtime insulin dose per day of 0.13 mL and 0.10 mL, respectively. While the recommended quantity of mealtime insulin per day differs by patient, these levels are significantly lower than would be expected in a group of patients with adequately managed type 2 diabetes using mealtime insulin [17, 18].
The Thomson Reuters MarketScan® research databases are comprised of only adjudicated claims; this minimizes, but not completely removes, the risk of incomplete, missing, or miscoded claims impacting the study findings. Errors present are likely random and independent of the study outcomes and cohorts, further minimizing their potential impact on the study. A related and significant limitation is the lack of records involving services that do not drive a service payment. Lab values (including hemoglobin A1C), patient biometric measures, and a record of free insulin samples are some of the key missing data fields. Further, the database contains very little information regarding physician behavior, training, or patient instructions, making it impossible to investigate or control for physician-level factors, including physician tendencies to prescribe more or less insulin per visit.