<b>Association of Hospitalizations With Randomized Glycemia-Lowering Treatment in GRADE</b>
Authors: Daniel S. Hsia, Naji Younes, Alokananda Ghosh, Erin J. Kazemi, Heidi Krause-Steinrauf, John B. Buse, Chelsea Baker, Janet Brown-Friday, Elsa Diaz, Jamie Diner, Erik J. Groessl, Elizabeth A. Legowski, Cary N. Mariash, Andrea H. Waltje, Deborah J. Wexler, Catherine L. Martin, J.P. Crandall, M.D. McKee, S. Behringer-Massera, J. Brown-Friday, E. Xhori, K. Ballentine-Cargill, S. Duran, H. Estrella, S. Gonzalez de la torre, J. Lukin, L.S. Phillips, E. Burgess, D. Olson, M. Rhee, P. Wilson, T.S. Raines, J. Boers, J. Costello, M. Maher-Albertelli, R. Mungara, L. Savoye, C.A. White, C. Gullett, L. Holloway, F. Morehead, S. Person, M. Sibymon, S. Tanukonda, C. Adams, A. Ross, A. Balasubramanyam, R. Gaba, E. Gonzalez Hattery, A. Ideozu, J. Jimenez, G. Montes, C. Wright, P. Hollander, E. Roe, A. Jackson, A. Smiley, P. Burt, L. Estrada, K. Chionh, F. Ismail-Beigi, C. Falck-Ytter, L. Sayyed Kassem, A. Sood, M. Tiktin, T. Kulow, C. Newman, K.A. Stancil, B. Cramer, J. Iacoboni, M.V. Kononets, C. Sandsers, L. Tucker, A. Werner, A. Maxwell, G. McPhee, C. Patel, L. Colosimo, A. Krol, R. Goland, J. Pring, L. Alfano, P. Kringas, C. Hausheer, J. Tejada, K. Gumpel, A. Kirpitch, H. Schneier, J.B. Green, H. AbouAssi, R. Chatterjee, M.N. Feinglos, J. English Jones, S.A. Khan, J.B. Kimpel, R.P. Zimmer, M. Furst, B.M. Satterwhite, C.R. Thacker, K. Evans Kreider, C.N. Mariash, K.J. Mather, H.M. Ismail, A. Lteif, M. Mullen, T. Hamilton, N. Patel, G. Riera, M. Jackson, V. Pirics, D. Aguillar, D. Howard, S. Hurt, R. Bergenstal, A. Carlson, T. Martens, M. Johnson, R. Hill, J. Hyatt, C. Jensen, M. Madden, D. Martin, H. Willis, W. Konerza, S. Yang, K. Kleeberger, R. Passi, S. Fortmann, M. Herson, K. Mularski, H. Glauber, J. Prihoda, B. Ash, C. Carlson, P.A. Ramey, E. Schield, B. Torgrimson-Ojerio, K. Arnold, B. Kauffman, E. Panos, S. Sahnow, K. Bays, K. Berame, J. Cook, D. Ghioni, J. Gluth, K. Schell, J. Criscola, C. Friason, S. Jones, S. Nazarov, J. Barzilay, N. Rassouli, R. Puttnam, B. Ojoawo, R. Nelson, M. Curtis, B. Hollis, C. Sanders-Jones, K. Stokes, Z. El-Haqq, A. Kolli, T. Tran, D. Wexler, M.E. Larkin, J. Meigs, B. Chambers, A. Dushkin, G. Rocchio, M. Yepes, B. Steiner, H. Dulin, M. Cayford, K. Chu, A. DeManbey, M. Hillard, K. Martin, N. Thangthaeng, L. Gurry, R. Kochis, E. Raymond, V. Ripley, C. Stevens, J. Park, V. Aroda, A. Ghazi, M. Magee, A. Ressing, A. Loveland, M. Hamm, M. Hurtado, A. Kuhn, J. Leger, L. Manandhar, F. Mwicigi, O. Sanchez, T. Young, R. Garg, V. Lagari-Libhaber, H.J. Florez, W.M. Valencia, J. Marks, S. Casula, L. Oropesa-Gonzalez, L. Hue, A. Cuadot, R. Nieto-Martinez, A.K. Riccio Veliz, M. Gutt, Y.J. Kendal, B. Veciana, A. Ahmann, D. Aby-Daniel, F. Joarder, V. Morimoto, C. Sprague, D. Yamashita, N. Cady, N. Rivera-Eschright, P. Kirchhoff, B. Morales Gomez, J. Adducci, A. Goncharova, S.H. Hox, H. Petrovitch, M. Matwichyna, V. Jenkins, L. Broadwater, R.R. Ishii, N.O. Bermudez, D.S. Hsia, W.T. Cefalu, F.L. Greenway, C. Waguespack, E. King, G. Fry, A. Dragg, B. Gildersleeve, J. Arceneaux, N. Haynes, A. Thomassie, M. Pavlionis, B. Bourgeois, C. Hazlett, S. Mudaliar, R. Henry, S. Boeder, J. Pettus, E. Diaz, D. Garcia-Acosta, S. Maggs, C. DeLue, A. Stallings, E. Castro, S. Hernandez, J. Krakoff, J.M. Curtis, T. Killean, M. Khalid, E. Joshevama, E. Diaz, D. Martin, K. Tsingine, T. Karshner, J. Albu, F.X. Pi-Sunyer, S. Frances, C. Maggio, E. Ellis, J. Bastawrose, X. Gong, M.A. Banerji, P. August, M. Lee, D. Lorber, N.M. Brown, D.H. Josephson, L.L. Thomas, M. Tsovian, A. Cherian, M.H. Jacobson, M.M. Mishko, M.S. Kirkman, J.B. Buse, J. Diner, J. Dostou, S. Machineni, L. Young, K. Bergamo, A. Goley, J. Kerr, J.F. Largay, S. Guarda, J. Cuffee, D. Culmer, R. Fraser, H. Almeida, S. Coffer, E. Debnam, L. Kiker, S. Morton, K. Josey, G. Fuller, W.T. Garvey, A.L. Cherrington, D. Dyer, M.C.R. Lawson, O. Griffith, A. Agne, S. McCullars, R.M. Cohen, J. Craig, M.C. Rogge, K. Burton, K. Kersey, C. Wilson, S. Lipp, M.B. Vonder Meulen, C. Adkins, T. Onadeko, N. Rasouli, C. Baker, E. Schroeder, M. Razzaghi, C. Lyon, R. Penaloza, C. Underkofler, R. Lorch, S. Douglass, S. Steiner, W.I. Sivitz, E. Cline, L.K. Knosp, J. McConnell, T. Lowe, W.H. Herman, R. Pop-Busui, M.H. Tan, C. Martin, A. Waltje, A. Katona, L. Goodhall, R. Eggleston, S. Kuo, S. Bojescu, S. Bule, N. Kessler, E. LaSalle, K. Whitley, E.R. Seaquist, A. Bantle, T. Harindhanavudhi, A. Kumar, B. Redmon, J. Bantle, M. Coe, M. Mech, A. Taddese, K. Lesne, S. Smith, C. Desouza, L. Kuechenmeister, V. Shivaswamy, S. Burbach, M.G. Rodriguez, K. Seipel, A. Alfred, A.L. Morales, J. Eggert, G. Lord, W. Taylor, R. Tillson, D.S. Schade, A. Adolphe, M. Burge, E. Duran-Valdez, J. Martinez, A. Bancroft, S. Kunkel, F. Ali Jamaleddin Ahmad, D. Hernandez McGinnis, B. Pucchetti, E. Scripsick, A. Zamorano, R.A. DeFronzo, E. Cersosimo, M. Abdul-Ghani, C. Triplitt, D. Juarez, M. Mullen, R.I. Garza, H. Verastiqui, K. Wright, C. Puckett, P. Raskin, C. Rhee, S. Abraham, L.F. Jordan, S. Sao, L. Morton, O. Smith, L. Osornio Walker, L. Schnurr-Breen, R. Ayala, R.B. Kreymer, D. Sturgess, K.M. Utzschneider, S.E. Kahn, L. Alarcon-Casas Wright, E.J. Boyko, E.C. Tsai, D.L. Trence, S. Trikudanathan, B.N. Fattaleh, B.K. Montgomery, K.M. Atkinson, A. Kozedub, T. Concepcion, C. Moak, N. Prikhodko, S. Rhothisen, T.A. Elasy, S. Martin, L. Shackelford, R. Goidel, N. Hinkle, C. Lovell, J. Myers, J. Lipps Hogan, J.B. McGill, M. Salam, T. Schweiger, S. Kissel, C. Recklein, M.J. Clifton, W. Tamborlane, A. Camp, B. Gulanski, S.E. Inzucchi, K. Pham, M. Alguard, P. Gatcomb, K. Lessard, M. Perez, L. Iannone, E. Magenheimer, A. Montosa, J. Fradkin, H.B. Burch, A.A. Bremer, D.M. Nathan, J.M. Lachin, H. Krause-Steinrauf, N. Younes, I. Bebu, N. Butera, C.J. Buys, A. Fagan, Y. Gao, A. Ghosh, M.R. Gramzinski, S.D. Hall, E. Kazemi, E. Legowski, H. Liu, C. Suratt, M. Tripputi, A. Arey, M. Backman, J. Bethepu, C. Lund, P. Mangat Dhaliwal, P. McGee, E. Mesimer, L. Ngo, M. Steffes, J. Seegmiller, A. Saenger, V. Arends, D. Gabrielson, T. Conner, S. Warren, J. Day, J. Huminik, A. Scrymgeour, E.Z. Soliman, Y. Pokharel, Z.M. Zhang, C. Campbell, J. Hu, L. Keasler, S. Hensley, Y. Li, R. Mihalcea, D.J. Min, V. Perez-Rosas, L. Prosser, L. Resnicow, W. Ye, H. Shao, P. Zhang, J. Luchsinger, D. Sanchez, S. Assuras, E. Groessl, F. Sakha, H. Chong, N. Hillery, I. Abdouch, G. Bahtiyar, P. Brantley, F.E. Broyles, G. Canaris, P. Copeland, J.J. Craine, W.L. Fein, A. Gliwa, L. Hope, M.S. Lee, R. Meiners, V. Meiners, H. O’Neal, J.E. Park, A. Sacerdote, E. Sledge Jr, L. Soni, J. Steppel-Reznik, A. Turchin
Journal: Diabetes Care (2025)

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 &amp;gt;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.