Article: Optimization of Metformin in the GRADE Cohort: Effect on Glycemia and Body Weight
Authors: William I. Sivitz, Lawrence S. Phillips, Deborah J. Wexler, Stephen P. Fortmann, Anne W. Camp, Margaret Tiktin, Magalys Perez, Jacqueline Craig, Priscilla A. Hollander, Andrea Cherrington, Vanita R. Aroda, Meng Hee Tan, Jonathan Krakoff, Neda Rasouli, Nicole M. Butera, Naji Younes, the GRADE Research Group
Journal: Diabetes Care. 2020 Mar 5. pii: dc191769. doi: 10.2337/dc19-1769. [Epub ahead of print]
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.
Link to journal online: https://care.diabetesjournals.org/content/early/2020/02/27/dc19-1769.long