Optimization of Metformin in the GRADE Cohort: Effect on Glycemia and Body Weight
Author:
Sivitz William I.1ORCID, Phillips Lawrence S.23, Wexler Deborah J.4ORCID, Fortmann Stephen P.5, Camp Anne W.6, Tiktin Margaret7, Perez Magalys6, Craig Jacqueline8, Hollander Priscilla A.9ORCID, Cherrington Andrea10, Aroda Vanita R.11ORCID, Tan Meng Hee12, Krakoff Jonathan13, Rasouli Neda14, Butera Nicole M.15, Younes Naji15, Crandall Jill P., Diane McKee Melissa, Brown-Friday Janet, Xhori Entila, Ballentine-Cargill Keisha, Duran Sally, Lukin Jennifer, Beringher Stephanie, Gonzalez de la torre Susana, Phillips Lawrence, Burgess Elizabeth, Olson Darin, Rhee Mary, Wilson Peter, Stephanie Raines Tasha, Costello Julie, Gullett Chona, Maher-Albertelli Maxine, Morehead Folayan, Mungara Radhika, Person Saranjit, Savoye Louise, Sibymon Mabil, Tanukonda Sridhar, Ann White Carol, Holloway Leah, Adams Cynthia, Ross April, Balasubramanyam Ashok, Gonzalez Erica, Wright Charlyne, Hollander Priscilla, Roe Erin, Uy Analyn, Burt Polly, Estrada Lorie, Chionh Kris, Ismail-Beigi Faramarz, Falck-Ytter Corinna, Sayyed Kassem Laure, Sood Ajay, Tiktin Margaret, Cramer Bethany, Iacoboni Jacalyn, Kononets Maria V., Kulow Tanya, Newman Cynthia, Stancil Katherine A., Sanders Cristina, Tucker Lisa, Werner Amanda, Krol Adrienne, McPhee Gloria, Patel Christine, Colosimo Linda, Goland Robin, Pring James, Kringas Patricia, Tejada Jessica, Hausheer Camille, Schneier Harvey, Gumpel Kelly, Kirpitch Amanda, Green Jennifer B., AbouAssi Hiba, Chatterjee Ranee, Feinglos Mark N., English Jones Jennifer, Khan Shubi A., Kimpel Jeanne B., Zimmer Ronna P., Furst Mary, Satterwhite Barbara M., Thacker Connie R., Evans Kreider Kathryn, Mather Kieren J., Lteif Amale, Hamilton Tonya, Patel Nick, Riera Gabriela, Jackson Marcia, Pirics Vivian, Howard Devin, Aguillar Danielle, Hurt Sloan, Bergenstal Richard, Carlson Anders, Martens Thomas, Johnson Mary, Hill Renae, Hyatt Jamie, Jensen Connie, Madden Marcia, Martin Dianna, Willis Holly, Konerza Wanda, Passi Rebecca, Kleeberger Kathleen, Fortmann Stephen, Herson Michael, Mularski Karen, Glauber Harry, Prihoda James, Ash Britt, Carlson Christina, Anne Ramey Phyllis, Schield Emily, Torgrimson-Ojerio Britta, Arnold Kathy, Kauffman Bryan, Panos Elease, Sahnow Samantha, Bays Kristi, Cook Jennifer, Gluth Jennifer, Sasaki Debra, Schell Katrina, Criscola Jennifer, Friason Camille, Jones Suzi, Nazarov Sergey, Barzilay Joshua, Rassouli Negah, Puttnam Rachel, Curtis Michelle, Stokes Kia, Hollis Bonita, Sanders-Jones Cynthia, Nelson Roslin, El-Haqq Zakiah, Kolli Abby, Tran Tu, Wexler Deborah, Mary Larkin, Meigs James, Dushkin Amy, Rocchio Gianna, Chambers Brittany, Yepes Mike, Steiner Barbara, Dulin Hilary, Cayford Melody, DeManbey Andrea, Gurry Lindsey, Hillard Mallory, Martin Kimberly, Stevens Christine, Thangthaeng Nopporn, Kochis Raquel, Raymond Elyse, Ripley Valerie, Park Jean, Aroda Vanita, Ghazi Adline, Loveland Amy, Hurtado Maria, Kuhn Alexander, Mofor Florence, Florez Hermes J., Valencia Willy Marcos, Marks Jennifer, Oropesa-Gonzalez Lisset, Riccio Veliz Ana K., Nieto-Martinez Ramfis, Gutt Miriam, Ahmann Andrew, Aby-Daniel Diana, Joarder Farahnaz, Morimoto Victoria, Sprague Carol, Yamashita Daisuke, Cady Nancy, Kirchhoff Patricia, Rivera-Eschright Nadia, Adducci Joseph, Gomez Brianna M., Goncharova Alina, Hox Sophia H., Petrovitch Helen, Matwichyna Michael, Jenkins Victoria, Bermudez Nina O., Ishii Renée R., Hsia Daniel S., Cefalu William T., Greenway Frank L., Waguespack Celeste, King Erin, Haynes Natalie, Thomassie Amy, Bourgeois Brandi, Hazlett Claire, Henry Robert, Mudaliar Sunder, Boeder Schafer, Pettus Jeremy, Diaz Elsa, DeLue Catherine, Castro Erick, Hernandez Sylvia, Krakoff Jonathan, Curtis Jeffrey M., Killean Tina, Joshevama Erica, Diaz Enrique, Martin Denelle, Karshner Tracey, Albu Jeanine, Pi-Sunyer F. Xavier, Frances Sylvaine, Maggio Carol, Ellis Emily, Bastawrose Joseph, Gong Xiuqun, Ann Banerji Mary, August Phyllis, Lorber Daniel, Brown Necole M., Josephson Debra H., Thomas Lorraine L., Tsovian Mari, Cherian Ajini, Jacobson Marlo H., Mishko Motria M., Kirkman M. Sue, Bergamo Katherine, Buse John B., Dostou Jean, Young Laura, Goley April, Kerr Jeffrey, Largay Joseph F., Guarda Sonia, Cuffee Juanita, Culmer Dawn, Fraser Rachael, Almeida Hope, Coffer Samantha, Debnam Elizabeth, Kiker Lauren, Morton Sarah, Josey Kim, Fuller Gail, Garvey W. Timothy, Cherrington Andrea, Golson Dana, Griffith Olivia, Catherine Robertson Mary, Agne April, McCullars Steve, Cohen Robert M., Craig Jacqueline, Kersey Kimberly, Rogge M. Colleen, Wilson Carla, Burton Kathryn, Lipp Sonia, Vonder Meulen Mary Beth, Rasouli Neda, Schroeder Emily, Steiner Stephanie, Baker Chelsea, Underkofler Chantal, Douglass Sara, Sivitz William, Cline Erin, Knosp Laura, McConnell Jennifer, Lowe Tamara, Herman William H., Pop-Busui Rodica, Tan Meng H., Martin Catherine, Waltje Andrea, Goodhall Lynn, Eggleston Rebecca, Kuo Shihchen, Bule Stephanie, Kessler Nancy, LaSalle Elizabeth, Seaquist Elizabeth R., Bantle Anne, Kumar Anjali, Redmon Bruce, Bantle John, Harindhanavudhi Tasma, Coe Mary, Mech Michael, Taddese Abdisa, Lesne Lesia, Smith Shannon, Desouza Cyrus, Kuechenmeister Lisa, Shivaswamy Vijay, Laura Morales Ana, Rodriguez Maria Grace, Seipel Kris, Alfred Alissa, Eggert Jenna, Lord Grace, Taylor William, Tillson Renee, Schade David S., Adolphe Allen, Burge Mark, Duran-Valdez Elizabeth, Martinez Janae, McGinnis Doris Hernandez, Pucchetti Benjamin, Scripsick Elizabeth, DeFronzo Ralph A., Cersosimo Eugenio, Abdul-Ghani Muhammad, Triplitt Curtis, Verastiqui Hector, Irene Garza Rosa, Wright Kathryn, Puckett Curtiss, Raskin Philip, Rhee Chanhaeng, Abraham Soma, Fan Jordan Lin, Sao Serey, Morton Luisa, Smith Oralenda, Osornio Walker Laura, Schnurr-Breen Laura, Ayala Rosa, Brian Kraymer Robert, Sturgess Daytheon, Utzschneider Kristina M., Kahn Steven E., Alarcon-Casas Wright Lorena, Boyko Edward J., Tsai Elaine C., Trence Dace L., Fattaleh Basma N., Montgomery Brenda K., Atkinson Karen M., Concepcion Tessa, Kozedub Alexandra, Moak Cameron, Rhothisen Samantha, Elasy Tom A., Martin Stephanie, Shackelford Laura, Goidel Rita, Hinkle Nina, Lipps Hogan Janie, Lovell Cynthia, Myers Janet, McGill Janet B., Salam Maamoun, Kissel Sarah, Schweiger Toni, Recklein Carol, Tamborlane William, Gatcomb Patricia, Camp Anne, Gulanski Barbara, Inzucchi Silvio, Pham Kim, Alguard Michele, Lessard Katarzyna, Perez Magalys, Magenheimer Elizabeth, Montoza Abmaridel, Nathan David M., Lachin John, Buse John B., Kahn Steven E., Krause-Steinrauf Heidi, Larkin Mary, Tiktin Margaret, Wexler Deborah, Burch Henry B., Linder Barbara, Bremer Andrew, Lachin John, Krause-Steinrauf Heidi, Younes Naji, Backman Michael, Bebu Ionut, Buys C. J., Fagan Murphy Anna, Gao Yuping, Gramzinski Michaela, Hall Stephanie, Legowski Elizabeth, Arey Alyssa, Bethepu Joel, Lund Claire, Mangat Dhaliwal Pam, McGee Paula, Mesimer Emily, Ngo Lisa, Steffes Michael, Seegmiller Jesse, Saenger Amy, Arends Valerie, Gabrielson Deanna, Conner Todd, Warren Stuart, Day Jolene, Scrymgeour Alexandra, Soliman Elsayed Z., Zhang Zhu-Ming, Campbell Charles, Hu Julie, Keasler Lisa, Hensley Susan, Li Yabing, Herman William, Martin Catherine, Waltje Andrea, Kuo Shihchen, Mihalcea Rada, Perez-Rosas Veronica, Prosser Lisa, Resnicow Kenneth, Ye Wen, Shao Hui, Zhang Ping, Luchsinger Jose, Sanchez Danurys, Burch Henry B., Bremer Andrew, Linder Barbara, Fradkin Judith, Groessl Erik, Chong Helen, Hillery Naomi, Abdouch Ivan, Brantley Paula, Broyles Frances E., Canaris Gay, Copeland Paul, Craine Jeri J., Fein Warren L., Lee Melissa S., Meiners Rebecca, Meiners Vaughn, O’Neal Hollis, Park James E., Sledge Edward, Steppel-Resnick Jeanne, Turchin Alexander, Brooks-Worrell Barbara, Hampe Christiane S., Newgard Christopher B., Palmer Jerry P., Shojaie Ali, Higgins John, Fischer Lawrence, Golden Sherita, Gonzalez Jeffery, Naik Aanand, Walker Elizabeth, Doner Lotenberg Lynne, Gallivan Joanne M., Lim Joanne, Tuncer Diane M., Behringer-Massera Stephanie,
Affiliation:
1. University of Iowa, Iowa City, IA 2. Atlanta VA Medical Center, Decatur, GA 3. Emory University School of Medicine, Atlanta, GA 4. Diabetes Clinical Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 5. Kaiser Permanente Northwest, Portland, OR 6. Fair Haven Community Health Care, New Haven, CT 7. Case Western Reserve University, Cleveland, OH 8. University of Cincinnati, Cincinnati, OH 9. Baylor Research Institute, Dallas, TX 10. University of Alabama, Birmingham, AL 11. MedStar Health Research Institute, Hyattsville, MD 12. University of Michigan, Ann Arbor, MI 13. Southwestern American Indian Center, Phoenix, AZ 14. University of Colorado, Denver, CO 15. Department of Biostatistics and Bioinformatics, The Biostatistics Center, Milken Institute School of Public Health, The George Washington University, Rockville, MD
Abstract
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 and HbA1c values ≥6.8% (51 mmol/mol). These findings may help guide efforts to optimize metformin therapy among persons with type 2 diabetes and suboptimal glycemic control.
Funder
National Institute of Diabetes and Digestive and Kidney Diseases
Publisher
American Diabetes Association
Subject
Advanced and Specialized Nursing,Endocrinology, Diabetes and Metabolism,Internal Medicine
Cited by
15 articles.
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