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, William Timothy Garvey, Alokananda Ghosh, Erin J. Kazemi, Heidi J Krause-Steinrauf, Andrew Ahmann, Janet Brown-Friday, Sabina Casula, Andrea Cherrington, Tom A. Elasy, Stephen P. Fortmann, Jonathan A. Krakoff, Sunder Raj D. 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, Claire Adams, Alyson C. Ross, Ashok Balasubramanyam, Ruchi Gaba, Erica G. Hattery, Adrienne Ideozu, J Jimenez, Guillermo Montes, Caroline E. Wright, Priscilla A. Hollander, Esther Roé, Andrew C. Jackson, Abbas Smiley, Paul 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, Benvon C. 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, Patricia Kringas, Camille Hausheer, Juan G. Tejada, Kelly Gumpel, A. Kirpitch, Harvey Schneier, Julie B. Green, Hiba AbouAssi, Ranee Chatterjee, MN Feinglos, J. English Jones, SA Khan, Jeanne B. Kimpel, R.P. Zimmer, Merrick L. Furst, Barbara M. Satterwhite, C.R. Thacker, Kathryn Evans Kreider, C.N. Mariash, K.J. Mather, HM Ismail, Aida Nadim 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. W. Hill, Jamie Hyatt, Camilla Jensen, Marcia Madden, Dianna C. Martin, Holly J Willis, Wanda Konerza, Shoua Yang, Kathleen Kleeberger, Ronald B. Passi, Stephen P. Fortmann, M. Herson, Karen Mularski, Harry S. Glauber, James Prihoda, B. Ash, Christopher S. Carlson, Phyllis Anne Ramey, Emily Schield, Britta N. Torgrimson-Ojerio, Kathleen A. Arnold, Brittany Kauffman, Elease Panos, Samantha Sahnow, K. Bays, K. Berame, Jennifer J. Cook, Debra Ghioni, Jennifer Gluth, Kathleen A. Schell, Jennifer Criscola, Camille Friason, Steve Jones, С. А. Назаров, Joshua I. Barzilay, N Rassouli, R. Puttnam, Bukkie Ojoawo, Randy S. Nelson, M Curtis, Bruce W. Hollis, Cynthia Sanders-Jones, Karen Yvonne Stokes, Zakiah El-Haqq, Aparna Kolli, Thao Tran, Deborah J. Wexler, Mary E. Larkin, James B. Meigs, B. Chambers, Alexander D. Dushkin, Gianna Rocchio, Manuel A Yepes, Barbara S. Steiner, Hilary Dulin, MELODY CAYFORD, Kon Chu, Andrea DeManbey, M. Hillard, Kimberly A. Martin, Nopporn Thangthaeng, L. Gurry, Raquel Kochis, Elizabeth G. Raymond, V. Ripley, Christine R. Stevens, Jaebum Park, Vanita R. Aroda, Ahmed Ghazi, Michelle Fischmann Magee, Ann Ressing, Amy Loveland, Michael W. Hamm, Maria Daniela Hurtado, Alexander Kuhn, J. Leger, Lumanti Manandhar, Florence Mwicigi, Olga Sánchez, T. Kue Young, Rajesh Garg, Victoria Lagari-Libhaber, H.J. Florez, W.M. Valencia, Jennifer B. Marks, Sabina Casula, Lisset Oropesa-Gonzalez, Louis Hue, Alain Cuadot, Ramfis E Nieto-Martínez, AK Riccio Veliz, Miriam Gutt, Yvette J Kendal, B. Veciana, Andrew Ahmann, Diana Aby-Daniel, Farahnaz S. Joarder, Victoria Morimoto, Christy L. Sprague, Daisuke Yamashita, Nathaniel C. Cady, Nadia Rivera-Eschright, P. G. Kirchhoff, Brianna Morales Gomez, Joseph E. Adducci, А. В. Гончарова, S.H. Hox, Helen Petrovitch, Michael Matwichyna, Victoria M. Jenkins, L. Broadwater, Renée R. Ishii, N.O. Bermudez, Daniel S. Hsia, WT Cefalu, FL Greenway, Celeste Waguespack, Emma King, G. Fry, A. Dragg, Bethany Gildersleeve, J. Arceneaux, Norrisa Haynes, Amy Thomassie, Mallory Pavlionis, Benjamin Bourgeois, Chad J. Hazlett, Sunder Raj D. Mudaliar, Robert E. Henry, S. Boeder, Jeremy Pettus, E Diaz, Daneila Garcia-Acosta, S. Maggs, Catherine DeLue, A. Stallings, Eva Martínez de Castro, Salvador Hernández, Jonathan A. Krakoff, J.M. Curtis, Tina Killean, Muhammad Faisal Khalid, Enrique Joshevama, E Diaz, Dianna C. Martin, Kaylee Tsingine, Tracey Karshner, Jeanine Albu, FX Pi-Sunyer, S. Enrech Frances, C. Maggio, Elizabeth M. Ellis, Joseph Bastawrose, Xiaoyan Gong, MA Banerji, Phyllis August, Marcelo Simonelli Lee, Daniel Lorber, Necole M. Brown, Debra H. Josephson, L.L. Thomas, Mari Tsovian, Anil V. Cherian, M.H. Jacobson, Motria M. Mishko, Marian Sue Kirkman, JB Buse, Jamie Diner, Jean M. Dostou, S. Machineni, Laura Young, K. Bergamo, April L. Goley, John Kerr, J.F. Largay, Suzete Nascimento Farias da Guarda, Juanita Cuffee, Dawn Culmer, Ross M. Fraser, Henrique A. Almeida, Samantha Coffer, Edward S. Debnam, L. Kiker, Suzanne Morton, Kim Josey, Gene B. Fuller, W.T. Garvey, A.L. Cherrington, Debra Sue Dyer, MCR Lawson, Obi L. Griffith, April A. Agne, Steve McCullars, Cohen Rm, Jacqueline Craig, M. Colleen Rogge, Kathryn J. Burton, Kathryn Kersey, Charlton Wilson, Sonia Lipp, MB Vonder Meulen, Christopher Adkins, Tolu Onadeko, N Rasouli, Charles Baker, Emily B. Schroeder, Mehdi Razzaghi, Corey Lyon, R Peñaloza, Chantal Underkofler, Rebecca Lorch, S Douglass, Susanne Steiner, W.I. Sivitz, Elizabeth J. Cline, L.K. Knosp, Joseph R. McConnell, Tao Lu Lowe, WH Herman, Rodica Pop‐Busui, M H Tan, Catherine L. Martin, Andrea H. Waltje, András Katona, Lynn Goodhall, Rebecca Eggleston, Shihchen Kuo, Stefana Bojescu, S. Bule, N Kessler, Elizabeth R. LaSalle, Kennedy C. Whitley, Elizabeth R. Seaquist, A. Bantle, Tasma Harindhanavudhi, Anjali F Kumar, J. Bruce Redmon, John P. Bantle, Manuela Coe, Mario Mech, Abdisa Taddese, Laurence Lesne, Shannon D. Smith, Cyrus V Desouza, Lisa J. Kuechenmeister, V Shivaswamy, Susan Burbach, Maria Grace Rodriguez, Katja Seipel, Arun Alfred, A Meza Morales, Julia A. Eggert, G Lord, W. B. Taylor, Renee Tillson, DS Schade, Allen Adolphe, Mark R. Burge, Elizabeth Duran-Valdez, Jean Martínez, A. Bancroft, Steven L. Kunkel, F. Ali Jamaleddin Ahmad, Doris Hernandez McGinnis, Benjamin Pucchetti, Elizabeth Scripsick, A. Fernández Zamorano, RA DeFronzo, Eugênio Cersósimo, Muhammad A Abdul‐Ghani, Curtis L. Triplitt, D Taira Juarez, R.I. Garza, Hector Verastiqui, Kerry Wright, CURTISS L. PUCKETT, Philip Raskin, Choong Kyun Rhee, Susan C. Abraham, Lin Fan Jordan, Serey Sao, Lindsay McOmber Morton, Oliver Smith, Lynne Walker, L. Schnurr-Breen, Rosa María Ayala, Robert Brian Kreymer, David John 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, Cameron Moak, Nina Prikhodko, Samantha Rhothisen, TA Elasy, S Martin, Linda C. Shackelford, Rita Goidel, Nancy C. Hinkle, Christopher Roland Lovell, John Myers, Janie Lipps Hogan, J.B. McGill, Maamoun Salam, Toni L. Schweiger, Sandra Kissel, C. Recklein, M.J. Clifton, William V. Tamborlane, Andrew Steven Camp, Barbara Gulanski, SE Inzucchi, K. Pham, Michele Alguard, P. Gatcomb, K Lessard, M.J. Rubio Pérez, Lucio Iannone, Elizabeth A. Magenheimer, A. Montosa, WT Cefalu, JUDITH E. FRADKIN, H B Burch, AA Bremer, DM Nathan, DM Nathan, JM Lachin, JB Buse, SE Kahn, Heidi J Krause-Steinrauf, Mary E. Larkin, Margaret Tiktin, Deborah J. Wexler, H B Burch, AA Bremer, JM Lachin, Heidi J Krause-Steinrauf, Naji Younes, Ionut Bebu, NICOLE M. BUTERA, C.J. Buys, Anne M. Fagan, Ying Gao, Alokananda Ghosh, Michaela R. Gramzinski, S D Hall, Elham Kazemi, Elizabeth A Legowski, Haixia Liu, Colleen E. Suratt, Mark Tripputi, Alyssa Arey, Mattias Backman, J. Bethepu, Christian Have Lund, P Mangat Dhaliwal, Paula L. McGee, Emily Mesimer, Long Hoang Ngo, Michael W. Steffes, J. Edwin Seegmiller, Amy K. Saenger, Valerie L. Arends, Deanna Gabrielson, Therese Conner, Scott Warren, John Day, J. Huminik, A. Scrymgeour, EZ Soliman, Yashashwi Pokharel, Zhiming Zhang, Colin K. Campbell, Jingzhou Hu, Lisa Keasler, S Hensley, Y Li, WH Herman, Shihchen Kuo, Catherine L. Martin, Andrea H. Waltje, R. Mihalcea, D.J. Min, V. Perez-Rosas, Lisa A. Prosser, Ken Resnicow, Wei Ye, Hui Shao, Ping Zhang, Jose Alejandro Luchsinger, David Sánchez‐Infantes, Stephanie Assuras, Erik J. Groessl, Fatema Sakha, Hsu Pheen Chong, Naomi Hillery, Brendan M. Everett, Ivan Abdouch, Gül Bahtiyar, Phillip J. Brantley, FRANCES E. BROYLES, Gay J. Canaris, Paul M. Copeland, Jeri J. Craine, Warren L. Fein, Agnieska Gliwa, Lisel Hope, Myeong Soo Lee, Ryan J. Meiners, Vaughn Meiners, Hollis R. O’Neal, JE Park, Alan Scott Sacerdote, Edward 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...