Suboptimal Adherence to ACE Inhibitors, Statins in Adolescents With Type 1 Diabetes

boy giving himself insulin
Teenage boy taking insulin therapy
Although medication adherence to both angiotensin-converting enzyme inhibitors and statins is initially high in adolescents with type 1 diabetes, it frequently deteriorates over time.

Although medication adherence to both angiotensin-converting enzyme ACE inhibitors and statins is initially high in adolescents with type 1 diabetes, it frequently deteriorates over time, according to study results published in Diabetes Care.

Given a lack of data on adherence to adjunct noninsulin medications in adolescents with type 1 diabetes, researchers used data from the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial ( Identifier: NCT01581476), a multicenter, double-blind, randomized, placebo-controlled trial that included adolescents with type 1 diabetes in the United Kingdom, Canada, and Australia. Patients were instructed to take ACE inhibitors and statins daily or 2 corresponding placebos, and adherence was assessed with Medication Event Monitoring System (MEMS) devices on pill containers, as well as with pill counts.

The study cohort included 443 children and adolescents (203 girls) with type 1 diabetes aged 10 to 16 years. Patients were monitored for a median of 2.6 years. Adherence was assessed starting at 1 month after random treatment assignment and every 3 months thereafter for 2 to 4 years until completion of the trial.

Overall median adherence during the trial was 80.2% (interquartile range, 63.6%-91.8%) based on MEMS and 85.7% (interquartile range, 72.4%-92.9%) based on pill count. Adherence based on both MEMS and pill count dropped from 92.9% and 96.3% at the first visit, respectively, to 76.3% and 79.0% at the last visit (P <.001 for trend). The largest decline in adherence occurred during the first 18 months and remained mostly stable after that.

When the data were analyzed using different categories of adherence, the results indicated that most patients had a median adherence rate ≥75% during the trial period, but this rate decreased from 84% at the beginning of the study to between 56% and 58% after 18 to 24 months, and then to 53% after 48 months.

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In univariate linear regression models, baseline factors significantly associated with adherence were chronologic age (P =.03), with a lower adherence in older study participants; country of origin (P <.001), with the highest adherence reported in patients in Australia; and glycemic control (P <.001), with the lowest adherence linked to the highest hemoglobin A1c levels. In a multiple regression model, glycated hemoglobin level and country of origin remained independently associated with medication adherence (both P <.001).

The researchers acknowledged several study limitations, including limited adherence data for the population across the whole trial duration, possible limitations of the MEMS method to assess for adherence, missing data on socioeconomic status or psychosocial factors, and possible bias secondary to analyzing the data related to a selective group of patients who agreed to participate in this trial and were aware that medication adherence was monitored.

“Although type 1 diabetes is a complex condition, on the basis of the present data, the implementation of adjunct oral therapies in type 1 diabetes in the future seems feasible but will require specific strategies addressing potential barriers to adherence and ways of overcoming them,” stated the researchers.


Niechciał E, Acerini CL, Chiesa ST, et al. Medication adherence during adjunct therapy with statins and ACE inhibitors in adolescents with type 1 diabetes [published online February 27, 2020]. Diabetes Care. doi:10.2337/dc19-0884