We thank Drs. Rodbard and Karolicki for their commentary (1) to clarify key points related to the FullSTEP study discussed in our article (2), in particular, the use of self-titration algorithms to adjust prandial insulin dose. The FullSTEP (3) study and AUTONOMY (Study of Insulin Lispro in Participants With Inadequately Controlled Type 2 Diabetes) (2) trial highlight the importance of patient involvement in care and the effectiveness of self-titration of prandial insulin doses. In this regard, the two studies complement each other, supporting patient-centric approaches to insulin therapy intensification. We appreciate that the authors of FullSTEP have taken this opportunity to reinforce how a patient-centric approach to insulin therapy intensification can achieve improvements in blood glucose control. However, before the description in the commentary, the management of prandial insulin titration in the FullSTEP study (3,4) was not a primary emphasis, and we welcome the clarification that, indeed, FullSTEP used the same patient self-titration algorithms for adding mealtime insulin in both treatment arms (3). This patient self-titration algorithm was only very briefly mentioned and not described in the original article (3).
As the commentary indicates (1), there are important differences between the two studies. The primary efficacy measure of AUTONOMY assessed “the HbA1c change from baseline to the end of the study (week 24 after randomization) ... between Q3D and Q1D algorithms” (2). The primary outcome of FullSTEP assessed the “non-inferiority of stepwise addition of bolus insulin versus complete basal-bolus therapy, as assessed by change in HbA1c from baseline to 32 weeks” (3). The focus of the FullSTEP abstract (4) and article (3) compared the stepwise addition of mealtime insulin versus full basal-bolus therapy, and the AUTONOMY abstract (5) and article (2) compared two different patient self-titration algorithms for the stepwise addition of bolus insulin, with ∼44% of the trial site in primary care settings. For consistency and to enhance the initiation experience, the AUTONOMY trial began prandial insulin at breakfast, whereas the stepwise group in FullSTEP began at the largest meal, which could vary from day to day and between geographies. In addition, in the AUTONOMY trial, mealtime insulin was added at additional meals, in a progressive manner, when blood glucose targets were not achieved. Moreover, AUTONOMY had more than twice the number of patients randomized (1,106) versus the FullSTEP study (401) (2,3), and AUTONOMY was conducted as two separate studies under the same protocol to provide substantial evidence for the efficacy and safety of the sequential addition of mealtime insulin doses with patient self-titration algorithms (2).
As Rodbard and Karolicki (1) state, we too welcome the results from multiple studies like FullSTEP and AUTONOMY. Both studies demonstrate the importance of patient education and self-management in the effective escalation of insulin therapy to achieve improved patient outcomes.
Article Information
Duality of Interest. S.V.E. serves on an advisory board for Eli Lilly and is on a Lilly speakers’ board. S.V.E. has advised for Tandem, Merck, Boehringer Ingelheim, Bristol-Myers Squibb, Dexcom, Novo Nordisk, Sanofi, and Abbott. R.L., J.J., and L.C.G. are full-time employees of Eli Lilly and Company and are minor stock owners as part of an employee offering program. Writing assistance was provided by Eli Lilly and Company. No other potential conflicts of interest relevant to this article were reported.
