Date Published: February 13, 2019
Publisher: Public Library of Science
Author(s): Yunwen Xu, Scott J. Pilla, G. Caleb Alexander, Irene B. Murimi, Naeti Suksomboon.
Clinical guidelines recommend that metformin be continued after insulin is initiated among patients with type 2 diabetes, yet little is known regarding how often metformin or other non-insulin diabetes medications are continued in this setting.
We conducted a retrospective cohort study to characterize rates and use patterns of six classes of non-insulin diabetes medications: biguanides (metformin), sulfonylureas, thiazolidinediones (TZDs), glucagon-like peptide 1 receptor agonists (GLP1 receptor agonists), dipeptidyl peptidase 4 inhibitors (DPP4 inhibitors), and sodium-glucose co-transporter inhibitors (SGLT2 inhibitors), among patients with type 2 diabetes initiating insulin. We used the 2010–2015 MarketScan Commercial Claims and Encounters data examining 72,971 patients with type 2 diabetes aged 18–65 years old who initiated insulin and had filled a prescription for a non-insulin diabetes medication in the 90 days prior to insulin initiation. Our primary outcome was the proportion of patients refilling the various non-insulin diabetes medications during the first 90 days after insulin initiation. We also used time-to-event analysis to characterize the time to discontinuation of specific medication classes.
Metformin was the most common non-insulin medication used prior to insulin initiation (N = 53,017, 72.7%), followed by sulfonylureas (N = 25,439, 34.9%) and DPP4 inhibitors (N = 8,540, 11.7%). More than four out of five patients (N = 65,902, 84.7%) refilled prescriptions for any non-insulin diabetes medications within 90 days after insulin initiation. Within that period, metformin remained the most common medication with the highest continuation rate of 84.6%, followed by SGLT2 inhibitors (81.9%) and TZDs (79.3%). Sulfonylureas were the least likely medications to be continued (73.6% continuation) though they remained the second most common medication class used after insulin initiation. The median time to discontinuation varied by therapeutic class from the longest time to discontinuation of 26.4 months among metformin users to the shortest (3.0 months) among SGLT2 inhibitor users.
While metformin was commonly continued among commercially insured adults starting insulin, rates of continuation of other non-insulin diabetes medications were also high. Further studies are needed to determine the comparative effectiveness and safety of continuing insulin secretagogues and newer diabetes medications after insulin initiation.
Type 2 diabetes affects 30.3 million people in the United States and is a leading cause of morbidity and mortality.  Type 2 diabetes and its complications also pose enormous health and economic burdens, [2, 3] especially with respect to outpatient settings and prescription expenditures. Given the progressive nature of type 2 diabetes, many patients eventually will be treated with insulin, which accounts for a large and increasing proportion of treatment expenditures.
In this study, we used anonymized, administrative claims data from 2010–2015 to describe patterns of non-insulin diabetes medication use after insulin initiation among commercially insured U.S. adults. We found that in the first 90 days after insulin initiation, the vast majority of patients continued their previous non-insulin therapy, including 84.6% of patients continuing metformin and 78–82% of patients continuing newer diabetes medications. In addition, the vast majority of patients taking insulin secretagogues continued them after insulin initiation, with a median time to discontinuation of almost two years. As insulin becomes an increasingly common treatment for patients with type 2 diabetes,  these findings highlight the critical need for studies of the comparative effects of continuing versus stopping insulin secretagogues and newer diabetes medications after insulin is started.
Our analyses provide new insights into the use of diabetes medications after insulin initiation among commercially insured U.S. adults, calling for future studies to expand examinations to a more general population. Clinicians are highly adherent to the current treatment guidelines, which only address the use of metformin following the transition to insulin. The frequent continuation of other diabetes medications while initiating insulin therapy underscores the need for further research into diabetes treatment during the insulin transition to inform evidence-based guidelines that promote optimal management during this critical transition in care.