Optimization of Metformin in the GRADE Cohort: Effect on Glycemia and Body Weight

作者：William I. Sivitz, Lawrence S. Phillips, Deborah J. Wexler, Stephen P. Fortmann, Anne Camp, Margaret Tiktin, Magalys Perez, Jacqueline Craig, Priscilla Hollander, Andrea Cherrington, Vanita R. Aroda, Meng H. Tan, Jonathan Krakoff, Neda Rasouli, Nicole M. Butera, Naji Younes, Jill P. Crandall, M. Diane McKee, Janet Brown-Friday, Entila Xhori, Keisha Ballentine-Cargill, Sally Duran, Jennifer Lukin, Stephanie Beringher, Susana Gonzalez de la torre, Lawrence S. Phillips, Elizabeth Burgess, Darin E. Olson, Mary K. Rhee, Peter W.F. Wilson, Tasha Stephanie Raines, Julie Costello, Chona Gullett, Maxine Maher-Albertelli, Folayan Morehead, Radhika Mungara, Saranjit Person, Louise Savoye, Mabil Sibymon, Sridhar Tanukonda, Carol Ann White, Leah Holloway, Cynthia Adams, April Ross, Ashok Balasubramanyam, Erica Gonzalez, C. Wright, Priscilla Hollander, Erin Roe, Analyn Uy, 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, Robin Goland, James Pring, P. Kringas, Jéssica Tejada, Camille Hausheer, Harvey Schneier, Kelly Gumpel, Amanda Kirpitch, 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, Kieren J. Mather, Amale Lteif, 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, 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, Debra Sasaki, K. Schell, Jennifer Criscola, C. Friason, Suzi Jones, С. А. Назаров, Joshua I. Barzilay, N. Rassouli, Rachel Puttnam, Michelle Curtis, K. Stokes, B. Hollis, C. Sanders-Jones, Roslin Nelson, Z. El-Haqq, A. Kolli, Tú-Anh Tran, Deborah J. Wexler, Larkin Mary, James B. Meigs, Amy Dushkin, Gianna Rocchio, Brittany D. Chambers, Mike Yepes, Barbara Steiner, H. Dulin, M. Cayford, A. DeManbey, Lindsey Gurry, Mallory Hillard, Kimberly Martin, Christine Stevens, Nopporn Thangthaeng, R. Kochis, Elyse Raymond, Valerie Ripley, Jean Park, Vanita R. Aroda, Adline Ghazi, Amy Loveland, Maria D. Hurtado, Alexander Kuhn, Florence Mofor, Hermes Flórez, Willy Marcos Valencia, Jennifer B. Marks, Lisset Oropesa-Gonzalez, A.K. Riccio Veliz, Ramfis Nieto‐Martínez, M. Gutt, Andrew Ahmann, Diana Aby-Daniel, Farahnaz Joarder, Victoria Morimoto, C. Sprague, Daisuke Yamashita, Nancy Cady, P. Kirchhoff, N. Rivera-Eschright, Joseph Adducci, B. Morales Gomez, Аліна Гончарова, Sophia H. Hox, Helen Petrovitch, M. Matwichyna, Victoria Jenkins, Nina O. Bermudez, R.R. Ishii, Daniel S. Hsia, William T. Cefalu, Frank L. Greenway, C. Waguespack, Erin King, Natalie Haynes, A. Thomassie, Brandi Bourgeois, C. Hazlett, Robert R. Henry, Sunder Mudaliar, Schafer Boeder, Jeremy Pettus, Elsa Diaz, Catherine DeLue, Erick Castro, Sylvia Hernandez, Jonathan Krakoff, Jeffrey M. Curtis, Tina Killean, E. Joshevama, E. Diaz, Denelle Martin, T. Karshner, Jeanine Albu, F. Xavier Pi‐Sunyer, Sylvaine Frances, Carol A. Maggio, Emily Ellis, Joseph Bastawrose, Xiuqun Gong, Mary Ann Banerji, Phyllis August, Daniel Lorber, N.M. Brown, D.H. Josephson, Lorraine L. Thomas, M. Tsovian, A. Cherian, Marlo H. Jacobson, M.M. Mishko, M. Sue Kirkman, Katherine Bergamo, John B. Buse, Jean M. Dostou, Laura Young, 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 Golson, O. Griffith, Mary Catherine Robertson, April A. Agne, S. McCullars, Robert M. Cohen, Jacqueline Craig, K. Kersey, M.C. Rogge, Carla Wilson, Kathryn Burton, Sonia Lipp, Mary Beth Vonder Meulen, Neda Rasouli, Emily B. Schroeder, Stephanie Steiner, Chelsea Baker, Chantal Underkofler, Sara Douglass, 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, L. Goodhall, Rebecca Eggleston, Shihchen Kuo, Stephanie Bule, N. Kessler, Elizabeth LaSalle, Elizabeth R. Seaquist, A. Bantle, Anjali Kumar, J. Bruce Redmon, John P. Bantle, Tasma Harindhanavudhi, M. Coe, M. Mech, Abdisa Taddese, Lesia Lesne, Shannon D. Smith, Cyrus Desouza, Lisa Kuechenmeister, Vijay Shivaswamy, A.L. Morales, M.G. Rodriguez, K. Seipel, Alissa Alfred, J. Eggert, G. Lord, William Taylor, R. Tillson, David S. Schade, Allen Adolphe, Mark R. Burge, Elizabeth Duran-Valdez, Janae Martinez, D. Hernandez McGinnis, B. Pucchetti, E. Scripsick, Ralph A. DeFronzo, Eugênio Cersósimo, Muhammad Abdul-Ghani, Curtis Triplitt, H. Verastiqui, Rosa Irene Garza, 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, Rosa Ayala, Robert Brian Kraymer, D. Sturgess, Kristina M. Utzschneider, Steven E. Kahn, Lorena Alarcon-Casas Wright, Edward J. Boyko, Elaine C. Tsai, Dace Trence, Basma N. Fattaleh, Brenda K. Montgomery, Karen M. Atkinson, Tessa Concepcion, Alexandra Kozedub, C. Moak, S. Rhothisen, Tom A. Elasy, Stéphanie Martin, Laura Shackelford, R. Goidel, Nina Hinkle, J. Lipps Hogan, C. Lovell, Janet Myers, Janet B. McGill, Maamoun Salam, Sarah Kissel, Toni Schweiger, Carol Recklein, William V. Tamborlane, P. Gatcomb, Anne Camp, Barbara Gulanski, Silvio E. Inzucchi, Kim Pham, Michele Alguard, Katarzyna Lessard, Magalys Perez, Elizabeth Magenheimer, Abmaridel Montoza, David M. Nathan, John M. Lachin, John B. Buse, Steven E. Kahn, Heidi Krause‐Steinrauf, Mary Larkin, Margaret Tiktin, Deborah J. Wexler, Henry B. Burch, Barbara Linder, Andrew A. Bremer, John M. Lachin, Heidi Krause‐Steinrauf, Naji Younes, Michael Backman, Ionut Bebu, C.J. Buys, Anna Fagan Murphy, Yuping Gao, M.R. Gramzinski, Stephanie V. Hall, Elizabeth Legowski, A. Arey, 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, Alexandra Scrymgeour, Elsayed Z. Soliman, Zhu‐Ming Zhang, Charles Campbell, Julie Hu, Lisa Keasler, Susan Hensley, Yabing Li, William H. Herman, Catherine L. Martin, Andrea Waltje, Shihchen Kuo, Rada Mihalcea, Verónica Pérez‐Rosas, Lisa A. Prosser, Ken Resnicow, Wen Ye, Hui Shao, Ping Zhang, José A. Luchsinger, Danurys Sanchez, Henry B. Burch, Andrew A. Bremer, Barbara Linder, Judith Fradkin, Erik J. Groessl, Helen Chong, Naomi Hillery, I. Abdouch, P. Brantley, Frances E. Broyles, G. Canaris, Paul M. Copeland, J.J. Craine, W.L. Fein, Melissa S. Lee, R. Meiners, Vaughn Meiners, Hollis R. O’Neal, James E. Park, E. Sledge, Jeanne Steppel-Resnick, Alexander Turchin, Barbara Brooks‐Worrell, Christiane S. Hampe, Christopher B. Newgard, Jerry P. Palmer, Ali Shojaie, John Higgins, Lawrence Fischer, Sherita Hill Golden, Jeffery Gonzalez, Aanand D. Naik, Elizabeth A. Walker, Lynne Doner Lotenberg, Joanne Gallivan, Joanne Lim, Diane Tuncer, Stephanie Behringer-Massera · 发表于：Diabetes Care · 年份：2020 · DOI：10.2337/dc19-1769 · 被引用次数：27 · 研究领域：Diabetes Treatment and Management、Metabolism, Diabetes, and Cancer、Diabetes Management and Research

OBJECTIVE We evaluated the effect of optimizing metformin dosing on glycemia and body weight in type 2 diabetes. RESEARCH DESIGN AND METHODS This was a prespecified analysis of 6,823 participants in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) taking metformin as the sole glucose-lowering drug who completed a 4- to 14-week (mean ± SD 7.9 ± 2.4) run-in in which metformin was adjusted to 2,000 mg/day or a maximally tolerated lower dose. Participants had type 2 diabetes for <10 years and an HbA1c ≥6.8% (51 mmol/mol) while taking ≥500 mg of metformin/day. Participants also received diet and exercise counseling. The primary outcome was the change in HbA1c during run-in. RESULTS Adjusted for duration of run-in, the mean ± SD change in HbA1c was −0.65 ± 0.02% (−7.1 ± 0.2 mmol/mol) when the dose was increased by ≥1,000 mg/day, −0.48 ± 0.02% (−5.2 ± 0.2 mmol/mol) when the dose was unchanged, and −0.23 ± 0.07% (−2.5 ± 0.8 mmol/mol) when the dose was decreased (n = 2,169, 3,548, and 192, respectively). Higher HbA1c at entry predicted greater reduction in HbA1c (P < 0.001) in univariate and multivariate analyses. Weight loss adjusted for duration of run-in averaged 0.91 ± 0.05 kg in participants who increased metformin by ≥1,000 mg/day (n = 1,894). CONCLUSIONS Optimizing metformin to 2,000 mg/day or a maximally tolerated lower dose combined with emphasis on medication adherence and lifestyle can improve glycemia in type 2 diabetes...