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

• Type of Material: Article
• Authors: William I Sivitz, University of Iowa; Lawrence Phillips, Emory University; Deborah J Wexler, Harvard Medical School; Stehen P Fortmann, Kaiser Permanente Northwest; Anne W Camp, Fair Haven Community Health Care; Margaret Tiktin, Case Western Reserve University; Magalys Perez, Fair Haven Community Health Care; Jacqueline Craig, University of Cincinnati; Priscillia A Hollander, Baylor Research Institute; Andrea Cherrington, University of Alabama Birmingham; Vanita R Aroda, MedStar Health Research Institute; Meng Hee Tan, University of Michigan; Jonathan Krakoff, Southwestern American Indian Center; Neda Rasouli, University of Colorado; Nicole M Butera, George Washington University; Naji Younes, George Washington University
• Language: English
• Date: 2020-05-01
• Publisher: AMER DIABETES ASSOC
• Publication Version: Final Published Version
• Copyright Statement: © 2020 by the American Diabetes Association
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.2337/dc19-1769
• Title of Journal or Parent Work: DIABETES CARE
• Volume: 43
• Issue: 5
• Start Page: 940
• End Page: 947
• Grant/Funding Information: The GRADE Study is supported by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (U34-DK-088043 and U01-DK-098246). The American Diabetes Association supported the initial planning meeting for the U34 proposal. The National Heart, Lung, and Blood Institute and the Centers for Disease Control and Prevention are also providing funding support. Educational materials have been provided by the National Diabetes Education Program. Material support in the form of donated medications and supplies has been provided by BD Biosciences, Bristol-Myers Squibb, Merck, Novo Nordisk, Roche Diagnostics, and Sanofi.
• Keywords: MONOTHERAPY; WORLDWIDE STANDARDIZATION; Life Sciences & Biomedicine; Science & Technology; EFFICACY; Endocrinology & Metabolism; SAFETY; SITAGLIPTIN; INITIAL COMBINATION THERAPY; DOUBLE-BLIND; CONSENSUS STATEMENT; EXTENDED-RELEASE METFORMIN; VILDAGLIPTIN
• Research Categories: Health Sciences, Public Health

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.