Association of Hospitalizations With Randomized Glycemia-Lowering Treatment in GRADE

Daniel S. Hsia, Pennington Biomedical Research Center, Baton Rouge, LA.
Naji Younes, Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD.
Alokananda Ghosh, Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD.
Erin J. Kazemi, 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.
John B. Buse, Division of Endocrinology and Metabolism, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC.
Chelsea Baker, Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado School of Medicine, Aurora, CO.
Janet Brown-Friday, Endocrinology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY.
Elsa Diaz, VA San Diego Healthcare System, San Diego, CA.
Jamie Diner, Division of Endocrinology and Metabolism, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC.
Erik J. Groessl, VA San Diego Healthcare System, San Diego, CA.
Elizabeth A. Legowski, Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD.
Cary N. Mariash, Division of Endocrinology and Metabolism, Indiana University School of Medicine, Indianapolis, IN.
Andrea H. Waltje, University of Michigan, Ann Arbor, MI.
Deborah J. Wexler, Massachusetts General Hospital Diabetes Center, Harvard Medical School, Boston, MA.
Catherine L. Martin, University of Michigan, Ann Arbor, MI.

Document Type

Journal Article

Publication Date

5-27-2025

Journal

Diabetes care

DOI

10.2337/dc24-2839

Abstract

OBJECTIVE: To compare rates of and risk factors for hospitalizations among Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) participants taking metformin and randomly assigned to insulin glargine U-100, glimepiride, liraglutide, or sitagliptin. RESEARCH DESIGN AND METHODS: Intention-to-treat (ITT) (N = 5,047) and on-assigned-treatment (AT) (N = 4,830) data sets were used. Baseline differences between those hospitalized versus those not hospitalized were assessed. Kaplan-Meier analysis was used to determine incidence for time to first hospitalization, and log-rank tests were used to determine treatment group differences. Time-to-event analyses were used to examine factors affecting subsequent hospitalization risk. RESULTS: During GRADE, 1,636 participants (32.4%) were hospitalized at least once and 751 (14.9%) were hospitalized more than once. Hospitalized participants were older, less likely to be Hispanic, more likely to be White, and more likely to have a history of hypertension and had higher baseline BMI. There were no treatment group differences in incidence for time to first hospitalization in the ITT data set (P = 0.148), but a reduced hazard rate was observed for those taking liraglutide versus those taking glimepiride in the AT data set (hazard ratio 0.78 [95% CI 0.66, 0.92]; P = 0.022). Factors increasing the risk for subsequent hospitalizations included meeting the secondary outcome (HbA1c >7.5%, confirmed), each prior hospitalization, and change from assigned treatment (29%, 41%, and 56% increase in risk, respectively). Assignment to liraglutide versus glimepiride reduced this risk by 13%. CONCLUSIONS: Hospitalizations were common in GRADE, and rates were nearly identical across treatment groups. The small, but significant, reduction in risk for subsequent hospitalizations among participants assigned to liraglutide versus glimepiride may influence treatment decisions in populations similar to GRADE participants.

Department

Biostatistics and Bioinformatics

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