Association of Hospitalizations with Randomized Glycemia-Lowering Treatment in the GRADE Study

Objective: To compare rates of and risk factors for hospitalizations among 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) datasets were used. Baseline differences between those with vs. without hospitalizations were compared. Kaplan-Meier analysis and log-rank tests were used to determine the incidence of time-to-first hospitalization and treatment group differences, respectively. Time-to-event analyses examined factors affecting subsequent hospitalization risk.

Results: During GRADE, 1,636 participants (32.4%) had at least one hospitalization and 751 (14.9%) were hospitalized more than once. Hospitalized participants were older, less likely to be Hispanic, more likely to be White, more likely to have a history of hypertension, and had higher baseline BMI. There were no treatment group differences in the incidence of time-to-first hospitalization in the ITT dataset (p=0.148), but a reduced hazard rate (HR) was observed for those taking liraglutide vs. glimepiride in the AT dataset (HR 0.78, 95% CI [0.66, 0.92]; p=0.022). Factors increasing the risk for subsequent hospitalizations were 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 vs. glimepiride reduced this risk by 13%.

Conclusions: Hospitalizations were common in the GRADE study, and rates were nearly identical across treatment groups. The small, but significant reduction in risk for subsequent hospitalizations among participants assigned to liraglutide vs. glimepiride may influence treatment decisions in populations similar to GRADE.