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

Authors

• Jeffrey S. Gonzalez, Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY.
• Hui Wen, Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD.
• Nicole M. Butera, Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD.
• Diane Uschner, Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD.
• Heidi Krause-Steinrauf, Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD.
• Michaela R. Gramzinski, Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD.
• Deborah J. Wexler, Massachusetts General Hospital Diabetes Center and Harvard Medical School, Boston, MA.
• Helen Petrovitch, Department of Veterans Affairs Pacific Islands Health Care System, Honolulu, HI.
• Claire J. Hoogendoorn, Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY.
• Gladys Crespo-Ramos, Endocrinology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY.
• Caroline Presley, Division of Preventative Medicine, University of Alabama, Birmingham, AL.
• Basma Fattaleh, VA Puget Sound Health Care System, Seattle, WA.
• Violet Lagari, Miami VA Healthcare System and University of Miami, Miami, FL.
• Elizabeth A. Walker, Endocrinology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY.
• Andrea L. Cherrington, General Internal Medicine and Population Science, Department of Medicine, University of Alabama, Birmingham, AL.

Document Type

Journal Article

Publication Date

2-1-2026

Journal

Diabetes care

Volume

49

Issue

2

DOI

10.2337/dc25-2008

Abstract

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.

APA Citation

Gonzalez, Jeffrey S.; Wen, Hui; Butera, Nicole M.; Uschner, Diane; Krause-Steinrauf, Heidi; Gramzinski, Michaela R.; Wexler, Deborah J.; Petrovitch, Helen; Hoogendoorn, Claire J.; Crespo-Ramos, Gladys; Presley, Caroline; Fattaleh, Basma; Lagari, Violet; Walker, Elizabeth A.; and Cherrington, Andrea L., "Medication Adherence in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE)" (2026). GW Authored Works. Paper 8779.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/8779

Department

Biostatistics and Bioinformatics