Glucose-Lowering Medications, Glycemia, and Cognitive Outcomes

作者：José A. Luchsinger, Samuel P. Rosin, Erin J. Kazemi, Naji Younes, Colleen E. Suratt, Basma N. Fattaleh, Hermes Flórez, Jeffrey S. Gonzalez, Priscilla Hollander, Sophia H. Hox, Shihchen Kuo, Melissa S. Lee, Thomas W. Martens, Rodica Pop‐Busui, Elizabeth R. Seaquist, Andrea Waltje, Joshua I. Barzilay, Jill P. Crandall, M. Diane McKee, Stephanie Beringher-Massera, Janet Brown-Friday, Entila Xhori, Keisha Ballentine-Cargill, Sally Duran, H. Estrella, Susana Gonzalez de la torre, Jennifer Lukin, Lawrence S. Phillips, Elizabeth Burgess, Darin E. Olson, Mary K. Rhee, Peter W.F. Wilson, Tasha Stephanie Raines, Johanna Boers, Julie Costello, Maxine Maher-Albertelli, Radhika Mungara, Louise Savoye, CarolAnn White, Chona Gullett, Leah Holloway, Folayan Morehead, Saranjit Person, Mabil Sibymon, Sridhar Tanukonda, Cynthia Adams, April Ross, Ashok Balasubramanyam, Ruchi Gaba, Erica Gonzalez, A. Ideozu, Julizza Jimenez, Gabriela Montes, C. Wright, Priscilla Hollander, Erin Roe, Analyn Jackson, A. Smiley, Polly Burt, Lorie Estrada, Kris Chionh, Faramarz Ismail‐Beigi, Corinna Falck-Ytter, Laure Sayyed Kassem, A. K. Sood, Margaret Tiktin, Bethany Cramer, Jacalyn Iacoboni, Maria V. Kononets, Tanya Kulow, Cynthia Newman, Katherine A. Stancil, Cristina Sanders, Lisa Tucker, Amanda Werner, Adrienne Krol, Gloria McPhee, Christine Patel, Linda Colosimo, Audrey Maxwell, Robin Goland, James Pring, L. Alfano, P. Kringas, Camille Hausheer, Jéssica Tejada, Kelly Gumpel, Amanda Kirpitch, Harvey Schneier, Jennifer B. Green, Hiba AbouAssi, Ranee Chatterjee, Mark N. Feinglos, Jennifer English Jones, Shubi A. Khan, J.B. Kimpel, Ronna P. Zimmer, Mary Furst, B.M. Satterwhite, Connie R. Thacker, Kathryn Evans Kreider, Cary N. Mariash, Kieren J. Mather, Heba M. Ismail, Amale Lteif, M. Mullen, T. Hamilton, Nick C. Patel, G. Riera, Marcia Jackson, Vivian Pirics, D. Howard, Danielle Aguillar, S. Hurt, Richard M. Bergenstal, Anders L. Carlson, Thomas Martens, Mary L. Johnson, R. Hill, Jamie Hyatt, C. Jensen, M. Madden, Dianna C. Martin, Holly Willis, Wanda Konerza, Shoua Yang, Rebecca Passi, K. Kleeberger, Stephen P. Fortmann, M. Herson, Karen Mularski, Harry Glauber, J. Prihoda, Britt Ash, Christina Carlson, P.A. Ramey, E. Schield, Britta Torgrimson-Ojerio, Kathy Arnold, Bryan Kauffman, E. Panos, S. Sahnow, K. Bays, Jennifer Cook, J. Gluth, D. Ghioni, K. Schell, Jennifer Criscola, C. Friason, Suzi Jones, С. А. Назаров, Joshua I. Barzilay, N. Rassouli, Rachel Puttnam, Olubukola Ojoawo, Roslin Nelson, Michelle Curtis, B. Hollis, C. Sanders-Jones, K. Stokes, Z. El-Haqq, A. Kolli, Tú-Anh Tran, Deborah J. Wexler, Mary Larkin, James B. Meigs, Brittany D. Chambers, Amy Dushkin, Gianna Rocchio, Mike Yepes, Barbara Steiner, H. Dulin, M. Cayford, A. DeManbey, Mallory Hillard, Kimberly Martin, Nopporn Thangthaeng, Lindsey Gurry, R. Kochis, Elyse Raymond, Valerie Ripley, Christine Stevens, Jean Park, Vanita R. Aroda, Adline Ghazi, Michelle Magee, A. Ressing, Amy Loveland, M. Hamm, Maria D. Hurtado, Alexander Kühn, J. Leger, L. Manandhar, F. Mwicigi, Osirelis Sanchez, Theresa Young, Rajesh Garg, V. Lagari-Libhaber, Hermes Flórez, Willy Marcos Valencia, Jennifer Mark, Sabina Casula, Lisset Oropesa-Gonzalez, L. Hue, A. Cuadot, Ramfis Nieto‐Martínez, A.K. Riccio Veliz, M. Gutt, Y.J. Kendal, Bertha Veciana, Andrew Ahmann, Diana Aby-Daniel, Farahnaz Joarder, Victoria Morimoto, C. Sprague, Daisuke Yamashita, Nancy Cady, N. Rivera-Eschright, P. Kirchhoff, Brianna Morales Gonzalez, Joseph Adducci, Аліна Гончарова, Sophia H. Hox, Helen Petrovich, M. Matwichyna, Victoria Jenkins, L. Broadwater, R.R. Ishii, Nina O. Bermudez, Daniel S. Hsia, William T. Cefalu, Frank L. Greenway, C. Waguespack, Erin King, Greta Fry, Amber Dragg, B. Gildersleeve, Jennifer Arceneaux, Natalie Haynes, A. Thomassie, M. Pavlionis, Brandi Bourgeois, C. Hazlett, Sunder Mudaliar, H Robert, Schafer Boeder, Jeremy Pettus, Elsa Diaz, D. Garcia-Acosta, S. Maggs, Catherine DeLue, Andrea Stallings, Erick Castro, Sylvia Hernandez, Jonathan Krakoff, Jeffrey M. Curtis, Tina Killean, Meshall Khalid, E. Joshevama, E. Diaz, Denelle Martin, K. Tsingine, T. Karshner, Jeanine Albu, F. Xavier Pi‐Sunyer, Sylvaine Frances, Carol A. Maggio, Emily Ellis, Joseph Bastawrose, Xiuqun Gong, Mary Ann Banerji, Phyllis August, Melissa S. Lee, Daniel Lorber, Brown Necole M., D.H. Josephson, Lorraine L. Thomas, Maria Tsovian, A. Cherian, Marlo H. Jacobson, M.M. Mishko, Sue Kirkman, John B. Buse, J. Dostou, Sriram Machineni, Laura Young, Katherine Bergamo, April Goley, J. B. Kerr, Joseph F. Largay, S. Guarda, J. Cuffee, D. Culmer, Rachael Fraser, Hope Almeida, Samantha Coffer, E. Debnam, L. Kiker, Sarah U. Morton, K. Josey, Gail Fuller, W. Timothy Garvey, Andrea Cherrington, Dana Dyer, M.C.R. Lawson, O. Griffith, April A. Agne, S. McCullars, Robert M. Cohen, Jacqueline Craig, M.C. Rogge, Kathryn Burton, K. Kersey, Carla Wilson, Sonia Lipp, Mary Beth Vonder Meulen, Connie Adkins, T. Onadeko, Neda Rasouli, Chelsea Baker, Emily B. Schroeder, M. Razzaghi, Corey Lyon, Richard Peñaloza, Chantal Underkofler, R. Lorch, Sarah A. Douglass, Stephanie Steiner, William I. Sivitz, Erin Cline, L.K. Knosp, Jennifer McConnell, T. Lowe, William H. Herman, Rodica Pop‐Busui, Meng H. Tan, Catherine L. Martin, Andrea Waltje, Aimee Katona, L. Goodhall, Rebecca Eggleston, Shihchen Kuo, S. Bojescu, Stephanie Bule, N. Kessler, Elizabeth LaSalle, Kelly Whitley, Elizabeth R. Seaquist, A. Bantle, Tasma Harindhanavudhi, Anjali Kumar, J. Bruce Redmon, John P. Bantle, M. Coe, M. Mech, Abdisa Taddese, Lesia Lesne, Shannon D. Smith, Cyrus Desouza, Lisa Kuechenmeister, Vijay Shivaswamv, S. Burbach, M.G. Rodriguez, K. Seipel, Alissa Alfred, A.L. Morales, J. Eggert, G. Lord, William Taylor, R. Tillson, David S. Schade, Allen Adolphe, Mark R. Burge, Elizabeth Duran-Valdez, Janae Martinez, Anna Bancroft, Susan Kunkel, Fadi Ali Jamaleddin Ahmad, D. Hernandez McGinnis, B. Pucchetti, E. Scripsick, A. Zamorano, Ralph A. DeFronzo, Eugênio Cersósimo, Muhammad Abdul-Ghani, Curtis Triplitt, DEANNA JUAREZ, Rosa Irene Garza, H. Verastiqui, K. Wright, Curtiss Puckett, Philip Raskin, Chanhaeng Rhee, Soma Abraham, L.F. Jordan, S. Sao, L. Morton, Oralenda Smith, Laura Osornio Walker, Laura Schnurr-Breen, R. Ayala, R.B. Kreymer, D. Sturgess, Kristina M. Utzschneider, Steven E. Kahn, Lorena Alarcon-Casas Wright, Edward J. Boyko, Elaine C. Tsiai, Dace Trence, S. Trikudanathan, Basma N. Fattaleh, Brenda K. Montgomery, Karen M. Atkinson, Alexandra Kozedub, Tessa Concepcion, C. Moak, N. Prikhodko, S. Rhothisen, Tom A. Elasy, Stéphanie Martin, Laura Shackelford, R. Goidel, Nina Hinkle, C. Lovell, Janet Myers, J. Lipps Hogan, Janet B. McGill, Maamoun Salam, Toni Schweiger, Sarah Kissel, Carol Recklein, Mary Jane Clifton, William V. Tamborlane, Anne Camp, Barbara Gulanski, Silvio E. Inzucchi, Kim Pham, Michele Alguard, P. Gatcomb, Katarzyna Lessard, Magalys Perez, Lynne Iannone, Elizabeth Magenheimer, Abmaridel Montosa, William T. Cefalu, Judith Fradkin, Henry B. Burch, Andrew A. Bremer, David M. Nathan, John M. Lachin, Heidi Krause‐Steinrauf, Naji Younes, Ionut Bebu, Nicole M. Butera, C.J. Buys, Anna Fagan, Yuping Gao, Alokananda Ghosh, M.R. Gramzinski, Stephanie D. Hall, Erin Kazemi, Elizabeth Legowski, Haiyin Liu, Colleen E. Suratt, Mark Tripputi, A. Arey, Michael Backman, Joel Bethepu, Claire Lund, P. Mangat Dhaliwal, Paula McGee, E. Mesimer, Lisa Ngo, Michael W. Steffes, Jesse C. Seegmiller, Amy K. Saenger, Valerie Arends, Deanna Gabrielson, T. Conner, Stuart Warren, Jolene Day, Jeffrey Huminik, Alexandra Scrymgeour, Elsayed Z. Soliman, Yashashwi Pokharel, Zhu‐Ming Zhang, Charles Campbell, Julie Hu, Lisa Keasler, Susan Hensley, Yabing Li, Rada Mihalcea, Do June Min, Verónica Pérez‐Rosas, Lisa A. Prosser, Ken Resnicow, Wen Ye, Hui Shao, Ping Zhang, José A. Luchsinger, Danurys Sanchez, Stephanie Assuras, Erik J. Groessl, F. Sakha, Helen Chong, Naomi Hillery, I. Abdouch, Gul Bahityar, P. Brantley, Frances E. Broyles, G. Canaris, Paul M. Copeland, J.J. Craine, W.L. Fein, A Gliwa, Lisel M. Hope, Melissa S. Lee, R. Meiners, Vaughn Meiners, Hollis R. O’Neal, James E. Park, Alan Sacerdote, E. Sledge, Soni Lk, Jeanne Steppel‐Reznik, Alexander Turchin · 发表于：JAMA Internal Medicine · 年份：2025 · DOI：10.1001/jamainternmed.2025.1189 · 被引用次数：10 · 研究领域：Diabetes Treatment and Management、Dementia and Cognitive Impairment Research、Cancer-related cognitive impairment studies

Importance: Type 2 diabetes (T2D) is a risk factor for cognitive impairment. Whether the choice of the second-line glucose-lowering treatment added to metformin or glycemic control affects cognitive performance in T2D of relatively short duration (<10 years) is not known. Objective: To compare the relative effect of 4 classes of glucose-lowering medications that were randomly added to metformin on cognitive performance and to examine the association of longitudinal glycemic levels with cognitive performance. Design, Setting, and Participants: This randomized clinical trial (the GRADE study) was conducted at 36 clinical centers in the US and included 3721 participants with T2D with baseline and follow-up cognitive performance data. GRADE was implemented 2013 to 2021, and data for this study were analyzed from February 2024 to February 2025. Interventions: For the primary objective, the exposure was randomization of metformin-treated participants to receive long-acting insulin (insulin glargine U-100), sulfonylurea (glimepiride), glucagon-like peptide-1 receptor agonist (liraglutide), or dipeptidyl peptidase-4 inhibitor (sitagliptin). The secondary objective assessed time-weighted hemoglobin A1c levels over the follow-up period. Main Outcomes and Measures: The primary cognitive outcome was the Digit Symbol Substitution Test score; the secondary cognitive outcomes were the immediate and delayed recall in the Spanish English Verbal Learning Test and letter and category fluency te...