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Research & Publications

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

By May 1, 2020September 24th, 2020No Comments

LINK TO RESEARCH
https://pubmed.ncbi.nlm.nih.gov/32139384/

PUBLICATION
Diabetes Care

AUTHORS
William I Sivitz 1 ,
Lawrence S Phillips 2 3 ,
Deborah J Wexler 4 ,
Stephen P Fortmann 5 ,
Anne W Camp 6 ,
Margaret Tiktin 7 ,
Magalys Perez 6 ,
Jacqueline Craig 8 ,
Priscilla A Hollander 9 ,
Andrea Cherrington 10 ,
Vanita R Aroda 11 ,
Meng Hee Tan 12 ,
Jonathan Krakoff 13 ,
Neda Rasouli 14 ,
Nicole M Butera 15 ,
Naji Younes 15 ,
GRADE Research Group

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.

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