Quantifying the effect of metformin treatment and dose on glycemic control

Abstract

Objective: Metformin is the first-line oral medication recommended for glycemic control in patients with type 2 diabetes. We reviewed the literature to quantify the effect of metformin treatment on glycated hemoglobin (HbA(1c)) levels in all types of diabetes and examine the impact of differing doses on glycemic control.

Research design and methods: MEDLINE, EMBASE, and the Cochrane Library were searched from 1950 to June 2010 for trials of at least 12 weeks' duration in which diabetic patients were treated with either metformin monotherapy or as an add-on therapy. Data on change in HbA(1c) were pooled in a meta-analysis. Data from dose-comparison trials were separately pooled.

Results: A total of 35 trials were identified for the main analysis and 7 for the dose-comparison analysis. Metformin monotherapy lowered HbA(1c) by 1.12% (95% CI 0.92-1.32; I(2) = 80%) versus placebo, metformin added to oral therapy lowered HbA(1c) by 0.95% (0.77-1.13; I(2) = 77%) versus placebo added to oral therapy, and metformin added to insulin therapy lowered HbA(1c) by 0.60% (0.30-0.91; I(2) = 79.8%) versus insulin only. There was a significantly greater reduction in HbA(1c) using higher doses of metformin compared with lower doses of metformin with no significant increase in side effects.

Conclusions: Evidence supports the effectiveness of metformin therapy in a clinically important lowering of HbA(1c) used as monotherapy and in combination with other therapeutic agents. There is potential for using higher doses of metformin to maximize glycemic control in diabetic patients without increasing gastrointestinal effects.

Figure 1

Mean difference in change in HbA_1c of metformin treatment versus comparator (boxes) and pooled estimates (diamonds) calculated by the random-effects DerSimonian and Laird method, stratified by metformin monotherapy and metformin added to an oral antidiabetes medication. Horizontal bars and diamond widths denote 95% CIs, and box sizes indicate relative weight in the analysis. (A high-quality color representation of this figure is available in the online issue.)

Figure 2

Mean difference in change in HbA_1c of metformin added on to insulin versus placebo and insulin comparator (boxes) and pooled estimates (diamonds) calculated by the random-effects DerSimonian and Laird method, stratified by type of diabetes. Horizontal bars and diamond widths denote 95% CIs, and box sizes indicate relative weight in the analysis. (A high-quality color representation of this figure is available in the online issue.)

Figure 3

Mean difference (boxes) in change in HbA_1c of high dose metformin, combining trial arms allocated to at least 2,000 mg metformin, versus low dose metformin, combining trial arms allocated to 1,000–1,500 mg metformin, showing pooled estimates (diamonds) calculated by the random-effects DerSimonian and Laird method. Horizontal bars and diamond widths denote 95% CIs, and box sizes indicate relative weight in the analysis. (A high-quality color representation of this figure is available in the online issue.)