• Media type: E-Article
  • Title: Optimization of Metformin in the GRADE Cohort: Effect on Glycemia and Body Weight
  • Contributor: Sivitz, William I.; Phillips, Lawrence S.; Wexler, Deborah J.; Fortmann, Stephen P.; Camp, Anne W.; Tiktin, Margaret; Perez, Magalys; Craig, Jacqueline; Hollander, Priscilla A.; Cherrington, Andrea; Aroda, Vanita R.; Tan, Meng Hee; Krakoff, Jonathan; Rasouli, Neda; Butera, Nicole M.; Younes, Naji; Crandall, Jill P.; Diane McKee, Melissa; Brown-Friday, Janet; Xhori, Entila; Ballentine-Cargill, Keisha; Duran, Sally; Lukin, Jennifer; Beringher, Stephanie; [...]
  • Published: American Diabetes Association, 2020
  • Published in: Diabetes Care
  • Extent: 940-947
  • Language: English
  • DOI: 10.2337/dc19-1769
  • ISSN: 0149-5992; 1935-5548
  • Keywords: Advanced and Specialized Nursing ; Endocrinology, Diabetes and Metabolism ; Internal Medicine
  • Abstract: <jats:sec> <jats:title>OBJECTIVE</jats:title> <jats:p>We evaluated the effect of optimizing metformin dosing on glycemia and body weight in type 2 diabetes.</jats:p> </jats:sec> <jats:sec> <jats:title>RESEARCH DESIGN AND METHODS</jats:title> <jats:p>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 &amp;lt;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.</jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>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 &amp;lt; 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).</jats:p> </jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>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.</jats:p> </jats:sec>
  • Description: <jats:sec>
    <jats:title>OBJECTIVE</jats:title>
    <jats:p>We evaluated the effect of optimizing metformin dosing on glycemia and body weight in type 2 diabetes.</jats:p>
    </jats:sec>
    <jats:sec>
    <jats:title>RESEARCH DESIGN AND METHODS</jats:title>
    <jats:p>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 &amp;lt;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.</jats:p>
    </jats:sec>
    <jats:sec>
    <jats:title>RESULTS</jats:title>
    <jats:p>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 &amp;lt; 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).</jats:p>
    </jats:sec>
    <jats:sec>
    <jats:title>CONCLUSIONS</jats:title>
    <jats:p>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.</jats:p>
    </jats:sec>
  • Footnote:
  • Access State: Open Access