Medication Adherence in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE)

OBJECTIVE To address previous inconsistencies in reports of differential adherence to diabetes medications, we examined medication adherence and evaluated treatment group differences in a substudy of participants in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). RESEARCH DESIGN AND METHODS GRADE participants (type 2 diabetes duration 10 years, HbA1c 6.8%–8.5%, on metformin alone) were randomly assigned to add insulin glargine, glimepiride, liraglutide, or sitagliptin. Adherence was measured semiannually for 3 years using a validated three-item scale (0–100, lowest to highest adherence) in a substudy (N = 1,739). Analyses included evaluation of adherence over time and testing treatment group differences in adherence and in the association between adherence and primary (HbA1c ≥7.0%) and secondary (HbA1c 7.5%) glycemic outcomes. RESULTS Overall mean ± SD adherence (average of participant-level mean ± SD) was high over 3 years of follow-up at 88.7 ± 10.01, on a scale of 0–100, and decreased slightly by 3 years relative to baseline (−2.0 ± 14.7; P 0.0001). No intergroup differences were observed until 3 years, when adherence was 5% and 3% higher for the glimepiride and sitagliptin groups, respectively, than for liraglutide (both P 0.05). Over follow-up and across groups, a 10-point decrease in adherence was associated with 15% and 19% increased risk of reaching primary (HbA1c ≥7.0%) and secondary (HbA1c 7.5%) glycemic outcomes (both P 0.0001). Lower adherence was somewhat more predictive of the secondary outcome for those assigned to glargine or liraglutide, compared with glimepiride or sitagliptin (each P 0.05). No other comparisons were significant. CONCLUSIONS Medication adherence was consistently high in GRADE. Observed treatment group differences were small and of unclear clinical significance. Overall, lower adherence robustly predicted worsening glycemic control, highlighting the importance of ongoing assessment.