[Metformin for type-2 diabetes mellitus. Systematic review and meta-analysis]

A Sáenz Calvo, I Fernández Esteban, A Mataix Sanjuán, M Ausejo Segura, M Roqué, D Moher
Atencion Primaria 2005 September 15, 36 (4): 183-91

OBJECTIVE: To evaluate the efficacy of metformin against placebo, diet, oral anti-diabetics, or insulin in type 2 diabetes mellitus.

DESIGN: Systematic review.

DATA SOURCES: MEDLINE (1966-2003), EMBASE (1974-2003), LILACS (1986-2003), Cochrane library (Issue 3, 2003).

SELECTION OF STUDIES: 29 randomized clinical trials of metformin in monotherapy, with results on mortality, morbidity, and biochemistry. EXTRACTION OF DATA: RevMan 4 computer program. Two reviewers extracted the data and evaluated the quality.

MAIN VARIABLES: any clinical event related to diabetes (mortality, coronary disease, stroke, arterial disease, and retinopathy). Secondary variables: weight and biochemistry.

RESULTS: 29 clinical studies with 37 comparisons of metformin were analyzed (13 with sulphonylureas, 12 with placebo, 3 with diet, 3 with thiazolidinediones, 2 with alpha-glucosidase inhibitors, 2 with insulin, and 2 with meglitinides). Metformin was more beneficial than the sulphonylureas or insulin for any clinical event associated with diabetes (relative risk [RR]=0.78; 95% confidence interval [CI], 0.65-0.94) and than diet (RR=0.74; 95% CI, 0.60-0.90). Metformin decreased glycosylated hemoglobin A1 (weighted mean difference, -1.21%; 95% CI, -1.48 to -0.94), low density lipoprotein cholesterol (weighted mean difference, -0.24; 95% CI, -0.40 to -0.09), and weight (standardized mean difference, -0.11; 95% CI, -0.18 to -0.04). Metformin was more beneficial than the placebo, diet or the thiazolidinediones on glycosylated hemoglobin A1, and than the sulphonylureas or insulin on weight.

CONCLUSIONS: In the long term metformin reduces the risks of clinical events associated with diabetes. There are no long term clinical trials which compare alpha-glucosidase inhibitors, meglitinides, and thiazolidinediones with metformin, in primary results. The different treatments compared with metformin did not obtain more benefit for the secondary results evaluated.

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