Weight Gain Was Associated With Worsening Glycemia and Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes Independent of Diabetes Medication in the GRADE Randomized Controlled Trial

作者：Deborah J. Wexler, W. Timothy Garvey, Alokananda Ghosh, Erin J. Kazemi, Heidi Krause‐Steinrauf, Andrew Ahmann, Janet Brown-Friday, Sabina Casula, Andrea Cherrington, Tom A. Elasy, Stephen P. Fortmann, Jonathan Krakoff, Sunder Mudaliar, Margaret Tiktin, Naji Younes, J.P. Crandall, Marc D. McKee, Stephanie Behringer-Massera, Janet Brown-Friday, Entila Xhori, Keisha Ballentine-Cargill, S Duran, H. Estrella, S. Gonzalez de la torre, Jennifer Lukin, Phillips Ls, Elizabeth Burgess, Darin E. Olson, Moo‐Yong Rhee, Peter W.F. Wilson, T.S. Raines, James E. Boers, Josh Costello, Maxine Maher-Albertelli, R. Mungara, Louise Savoye, Christine A. White, Chona Gullett, Leah Holloway, Folayan Morehead, Sharina D. Person, Mabil Sibymon, Sridhar Tanukonda, C. Adams, Alyson Ross, Ashok Balasubramanyam, Ruchi Gaba, Erica G. Hattery, A. Ideozu, J Jimenez, Guillermo Montes, Caroline Wright, Priscilla Hollander, Esther Roé, A. Jackson, Abbas Smiley, P. E. BURT, L Estrada, Kris Chionh, Faramarz Ismail‐Beigi, Corinna Falck-Ytter, L. Sayyed Kassem, Anil K. Sood, Margaret Tiktin, T. Kulow, Christopher L. Newman, K.A. Stancil, B. Cramer, Jacalyn Iacoboni, M.V. Kononets, C Sanders, Larry A. Tucker, A Werner, Adam D. Maxwell, Gloria McPhee, Chandni Patel, Linda Colosimo, Aleksandra Król, Robin Goland, James Pring, Lindsay N. Alfano, P. Kringas, Camille Hausheer, Juan Tejada, Kelly Gumpel, A. Kirpitch, Harvey Schneier, Julie Green, Hiba AbouAssi, Ranee Chatterjee, MN Feinglos, J. English Jones, SA Khan, J.B. Kimpel, R.P. Zimmer, Merrick L. Furst, B.M. Satterwhite, C.R. Thacker, Kathryn Evans Kreider, C.N. Mariash, K.J. Mather, HM Ismail, Aida Lteif, Tiffani K. Hamilton, N. Patel, G. Riera, Malaka B. Jackson, Vivian Pirics, Danielle Aguillar, Danielle Howard, Stephen D. Hurt, Richard M. Bergenstal, Anders L. Carlson, Thomas W. Martens, Mark W. Johnson, Richard J. Hill, Jamie Hyatt, Camilla Jensen, M. Madden, Dianna C. Martin, Holly Willis, Wanda Konerza, Shoua Yang, K. Kleeberger, Ronald B. Passi, Stephen P. Fortmann, M. Herson, Karen Mularski, Harry Glauber, J. Prihoda, B. Ash, Christopher S. Carlson, P.A. Ramey, E. Schield, Britta Torgrimson-Ojerio, Kathleen Arnold, Brittany Kauffman, E. Panos, S. Sahnow, K. Bays, K. Berame, Jennifer Cook, D. Ghioni, J. Gluth, Kathleen Schell, Jennifer Criscola, C. Friason, Steve Jones, С. А. Назаров, Joshua I. Barzilay, N Rassouli, R. Puttnam, B. Ojoawo, Randy Nelson, M Curtis, Bruce W. Hollis, C. Sanders-Jones, Karen Y. Stokes, Z. El-Haqq, Aparna Kolli, Thao Tran, Deborah J. Wexler, Mary Larkin, James B. Meigs, B. Chambers, Alexander Dushkin, Gianna Rocchio, Manuel Yepes, Barbara Steiner, H. Dulin, M. Cayford, Kon Chu, A. DeManbey, M. Hillard, Kimberly Martin, Nopporn Thangthaeng, L. Gurry, R. Kochis, Elizabeth G. Raymond, V. Ripley, Christine Stevens, Jaebum Park, Vanita R. Aroda, Ahmed Ghazi, Michelle Magee, A. Ressing, Amy Loveland, Michael W. Hamm, Maria D. Hurtado, Alexander Kuhn, J. Leger, Lumanti Manandhar, F. Mwicigi, Olga Sánchez, T. Kue Young, Rajesh Garg, V. Lagari-Libhaber, H.J. Florez, W.M. Valencia, Jennifer B. Marks, Sabina Casula, Lisset Oropesa-Gonzalez, Louis Hue, A. Cuadot, Ramfis Nieto‐Martínez, AK Riccio Veliz, M. Gutt, Y.J. Kendal, B. Veciana, Andrew Ahmann, Diana Aby-Daniel, F Joarder, Victoria Morimoto, Christy L. Sprague, Daisuke Yamashita, Nathaniel C. Cady, N. Rivera-Eschright, P. G. Kirchhoff, B. Morales Gomez, Joseph Adducci, А. В. Гончарова, S.H. Hox, Helen Petrovitch, M. Matwichyna, Victoria Jenkins, L. Broadwater, R.R. Ishii, N.O. Bermudez, Daniel S. Hsia, WT Cefalu, FL Greenway, C. Waguespack, Emma King, G. Fry, A. Dragg, B. Gildersleeve, J. Arceneaux, Norrisa Haynes, A. Thomassie, M. Pavlionis, B. Bourgeois, Chad Hazlett, Sunder Mudaliar, Robert E. Henry, S. Boeder, Jeremy Pettus, E Diaz, D. Garcia-Acosta, S. Maggs, Catherine DeLue, A. Stallings, E. Castro, Salvador Hernández, Jonathan Krakoff, J.M. Curtis, Tina Killean, Muhammad Khalid, Enrique Joshevama, E Diaz, Dianna C. Martin, K. Tsingine, T. Karshner, Jeanine Albu, FX Pi-Sunyer, S. Enrech Frances, C. Maggio, Elizabeth Ellis, Joseph Bastawrose, Xiaoyan Gong, MA Banerji, Phyllis August, M Lee, Daniel Lorber, N.M. Brown, D.H. Josephson, L.L. Thomas, M. Tsovian, Anil Cherian, M.H. Jacobson, M.M. Mishko, M. Sue Kirkman, JB Buse, Jamie Diner, Jean M. Dostou, S. Machineni, Laura Young, K. Bergamo, April Goley, John Kerr, J.F. Largay, Suzete Nascimento Farias da Guarda, J. Cuffee, D. Culmer, Ross M. Fraser, Henrique A. Almeida, Samantha Coffer, Edward S. Debnam, L. Kiker, Suzanne Morton, K. Josey, Gene B. Fuller, W.T. Garvey, A.L. Cherrington, Debra S. Dyer, MCR Lawson, Obi L. Griffith, April A. Agne, S. McCullars, Cohen Rm, Jacqueline Craig, M.C. Rogge, Kathryn Burton, Kathryn Kersey, Charlton Wilson, Sonia Lipp, MB Vonder Meulen, Christopher Adkins, T. Onadeko, N Rasouli, Charles Baker, Emily B. Schroeder, Mehdi Razzaghi, Corey Lyon, R Peñaloza, Chantal Underkofler, R. Lorch, S Douglass, Susanne Steiner, W.I. Sivitz, Elizabeth J. Cline, L.K. Knosp, Joseph R. McConnell, Tao L. Lowe, WH Herman, Rodica Pop‐Busui, M H Tan, Catherine L. Martin, Andrea Waltje, András Katona, L. Goodhall, Rebecca Eggleston, Shihchen Kuo, S. Bojescu, S. Bule, N Kessler, Elizabeth R. LaSalle, Kennedy C. Whitley, Elizabeth R. Seaquist, A. Bantle, Tasma Harindhanavudhi, Anjali Kumar, J. Bruce Redmon, John P. Bantle, Manuela Coe, Mario Mech, Abdisa Taddese, Laurence Lesne, Shannon D. Smith, Cyrus Desouza, Lisa Kuechenmeister, V Shivaswamy, S. Burbach, M.G. Rodriguez, Katja Seipel, Arun Alfred, A Meza Morales, Julia Eggert, G Lord, W. Taylor, R. Tillson, DS Schade, Allen Adolphe, Mark R. Burge, Elizabeth Duran-Valdez, Jean Martínez, A. Bancroft, Steven L. Kunkel, F. Ali Jamaleddin Ahmad, D. Hernandez McGinnis, B. Pucchetti, E. Scripsick, A. Zamorano, RA DeFronzo, Eugênio Cersósimo, Muhammad Abdul‐Ghani, Curtis Triplitt, D. Juarez, R.I. Garza, H. Verastiqui, Kerry Wright, Curtiss Puckett, P. Raskin, Choong Kyun Rhee, Susan C. Abraham, L.F. Jordan, S. Sao, Lindsay M. Morton, Oliver Smith, Lynne Walker, L. Schnurr-Breen, Rosa Ayala, R.B. Kreymer, David Sturgess, K.M. Utzschneider, SE Kahn, Lorena Alarcon-Casas Wright, Edward J. Boyko, EC Tsai, D.L. Trence, Subbulaxmi Trikudanathan, B.N. Fattaleh, B.K. Montgomery, K.M. Atkinson, Alexandra Kozedub, T. Concepcion, C. Moak, N. Prikhodko, S. Rhothisen, TA Elasy, S Martin, Linda Shackelford, R. Goidel, Nancy C. Hinkle, C. R. Lovell, John Myers, J. Lipps Hogan, J.B. McGill, Maamoun Salam, Toni Schweiger, Sandra Kissel, C. Recklein, M.J. Clifton, William V. Tamborlane, Andrew Camp, Barbara Gulanski, SE Inzucchi, K. Pham, Michele Alguard, P. Gatcomb, K Lessard, M.J. Rubio Pérez, Lucio Iannone, Elizabeth Magenheimer, A. Montosa, WT Cefalu, Judith Fradkin, H B Burch, AA Bremer, DM Nathan, DM Nathan, JM Lachin, JB Buse, SE Kahn, Heidi Krause‐Steinrauf, Mary Larkin, Margaret Tiktin, Deborah J. Wexler, H B Burch, AA Bremer, JM Lachin, Heidi Krause‐Steinrauf, Naji Younes, Ionut Bebu, NICOLE M. BUTERA, C.J. Buys, Anne M. Fagan, Ying Gao, Alokananda Ghosh, M.R. Gramzinski, S D Hall, Elham Kazemi, Elizabeth Legowski, Haixia Liu, Colleen E. Suratt, Mark Tripputi, A. Arey, Mattias Backman, J. Bethepu, Christian Lund, P Mangat Dhaliwal, Paula McGee, E. Mesimer, Long Ngo, Michael W. Steffes, J. Edwin Seegmiller, Amy K. Saenger, Valerie Arends, Deanna Gabrielson, Therese Conner, S. Warren, John Day, J. Huminik, A. Scrymgeour, EZ Soliman, Yashashwi Pokharel, Zhiming Zhang, Colin Campbell, Jingzhou Hu, Lisa Keasler, S Hensley, Y Li, WH Herman, Shihchen Kuo, Catherine L. Martin, Andrea Waltje, R. Mihalcea, D.J. Min, V. Perez-Rosas, Lisa A. Prosser, Ken Resnicow, Wei Ye, Hui Shao, Ping Zhang, José A. Luchsinger, David Sánchez‐Infantes, Stephanie Assuras, Erik J. Groessl, F. Sakha, Hsu Pheen Chong, Naomi Hillery, Brendan M. Everett, I. Abdouch, Gül Bahtiyar, Phillip J. Brantley, F.E. Broyles, G. Canaris, Paul M. Copeland, J.J. Craine, W.L. Fein, A Gliwa, Lisel Hope, Myeong Soo Lee, Ryan J. Meiners, Vaughn Meiners, Hollis R. O’Neal, JE Park, Alan Sacerdote, E. Sledge, Lina Soni, J. Steppel-Reznik, Alexander Turchin · 发表于：Diabetes Care · 年份：2025 · DOI：10.2337/dc24-2825 · 被引用次数：4 · 研究领域：Diabetes Treatment and Management、Bariatric Surgery and Outcomes、Diabetes, Cardiovascular Risks, and Lipoproteins

OBJECTIVE: Weight gain with glucose-lowering medications may interfere with effective type 2 diabetes (T2D) management. We evaluated weight change and the effect of weight gain on outcomes over 5 years on four diabetes medications. RESEARCH DESIGN AND METHODS: The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) randomized trial compared the addition of insulin glargine, glimepiride, liraglutide, or sitagliptin to metformin in participants with T2D. We report weight change and hazard ratio (HR) per kilogram of weight change for HbA1c >7.5%; cardiovascular disease (CVD), kidney disease, and neuropathy outcomes; and diabetes treatment satisfaction. RESULTS: Participants (n = 4,980) were 57 ± 10 years, 44% non-White, with HbA1c 7.5% ± 0.5%, and BMI 34.3 ± 6.8 kg/m2. Mean (95% CI) weight change (kg) during the first year was -3.5 (-3.8,-3.2) with liraglutide,-1.07 (-1.4,-0.78) with sitagliptin, 0.45 (0.16, 0.74) with glargine, and 0.89 (0.60, 1.2) with glimepiride (P < 0.0001). Thereafter, weight decreased in all groups. Weight gain within the first 6 months was associated with increased risk of HbA1c >7.5%, with modest differences by treatment, and with subsequent CVD (HR 1.03 [95% CI 1.005, 1.06]). Weight gain at 1 year was associated with increased risk of HbA1c >7.5% (HR 1.05 [1.04, 1.07]) and kidney disease (HR 1.03 [1.01, 1.06]). Baseline weight, but not weight gain, was associated with new-onset neuropathy. Weight gain was associated wit...