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Clinical Trial
. 2025 Jul 1;48(7):1288-1294.
doi: 10.2337/dc24-2839.

Association of Hospitalizations With Randomized Glycemia-Lowering Treatment in GRADE

Daniel S Hsia  1   2 , Naji Younes  3 , Alokananda Ghosh  3 , Erin J Kazemi  3 , Heidi Krause-Steinrauf  3 , John B Buse  4 , Chelsea Baker  5 , Janet Brown-Friday  6 , Elsa Diaz  7 , Jamie Diner  4 , Erik J Groessl  7   8 , Elizabeth A Legowski  3 , Cary N Mariash  9 , Andrea H Waltje  10 , Deborah J Wexler  11 , Catherine L Martin  10 ; GRADE Research Group
Collaborators, Affiliations
Clinical Trial

Association of Hospitalizations With Randomized Glycemia-Lowering Treatment in GRADE

Daniel S Hsia et al. Diabetes Care. .

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.

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Conflict of interest statement

Duality of Interest. D.S.H. reports contracts paid to his institution from Eli Lilly, Novo Nordisk, VIVUS, Moderna, and Takeda Development Center Americas/Emmes and personal consulting fees from Eli Lilly for the Pediatric Chronic Weight Management Portfolio. J.B.B. reports grant support paid to his institution from Bayer, Boehringer Ingelheim, Carmot Therapeutics, Corcept Therapeutics, Dexcom, Eli Lilly, Insulet, MannKind, Novo Nordisk, and vTv Therapeutics; consulting fees paid to his institution from Novo Nordisk; personal consulting fees from Alkahest, Altimmune, Anji Pharmaceutical, Aqua Medical, AstraZeneca, Boehringer Ingelheim, CeQur, Corcept Therapeutics, Eli Lilly, embecta, Fortress Biotech, GentiBio, Glyscend, Insulet, Mediflix, Medscape, Mellitus Health, Metsera, Moderna, Pendulum Therapeutics, Praetego, ReachMD, Stability Health, Tandem Diabetes Care, Terns Pharmaceuticals, and Vertex Pharmaceuticals; personal payment for expert testimony from Medtronic MiniMed; payment to his institution for expert testimony from Novo Nordisk; personal compensation for participation on a data safety monitoring board or advisory board for Altimmune, AstraZeneca, and Insulet; and stock or stock options for Glyscend, Mellitus Health, Pendulumn Therapeutics, Praetego, and Stability Health outside the submitted work. C.N.M. reports personal payment from Horizon Pharmaceuticals for participation in an advisory board meeting as a consultant. D.J.W. reports participation on a data monitoring committee for Novo Nordisk for the Semaglutide cardiOvascular oUtcomes trial (SOUL) and Evaluate Renal Function with Semaglutide Once Weekly (FLOW) trial of semaglutide outside the submitted work. No other potential conflicts of interest relevant to this article were reported.

References

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