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

MedStar author(s):
Citation: Diabetes Care. 43(5):940-947, 2020 05.PMID: 32139384Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Blood Glucose/de [Drug Effects] | *Body Weight/de [Drug Effects] | *Diabetes Mellitus, Type 2/dt [Drug Therapy] | *Hypoglycemic Agents/ad [Administration & Dosage] | *Metformin/ad [Administration & Dosage] | Adult | Aged | Blood Glucose/me [Metabolism] | Calibration | Comparative Effectiveness Research | Diabetes Mellitus, Type 2/bl [Blood] | Dose-Response Relationship, Drug | Drug Therapy, Combination | Female | Glycated Hemoglobin A/an [Analysis] | Glycated Hemoglobin A/me [Metabolism] | Humans | Hypoglycemic Agents/ae [Adverse Effects] | Insulin/aa [Analogs & Derivatives] | Insulin/ad [Administration & Dosage] | Insulin/ae [Adverse Effects] | Liraglutide/ad [Administration & Dosage] | Liraglutide/ae [Adverse Effects] | Male | Maximum Tolerated Dose | Metformin/ae [Adverse Effects] | Middle Aged | Sitagliptin Phosphate/ad [Administration & Dosage] | Sitagliptin Phosphate/ae [Adverse Effects] | Sulfonylurea Compounds/ad [Administration & Dosage] | Sulfonylurea Compounds/ae [Adverse Effects] | Weight Loss/de [Drug Effects] | Weight Loss/ph [Physiology]Year: 2020ISSN:
  • 0149-5992
Name of journal: Diabetes careAbstract: 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. Copyright (c) 2020 by the American Diabetes Association.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).All authors: Aroda VR, Butera NM, Camp AW, Cherrington A, Craig J, Fortmann SP, GRADE Research Group, Hollander PA, Krakoff J, Perez M, Phillips LS, Rasouli N, Sivitz WI, Tan MH, Tiktin M, Wexler DJ, Younes NOriginally published: Diabetes Care. 43(5):940-947, 2020 May.Fiscal year: FY2020Digital Object Identifier: ORCID: Date added to catalog: 2020-08-26
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Journal Article MedStar Authors Catalog Article 32139384 Available 32139384

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. Copyright (c) 2020 by the American Diabetes Association.

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).

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