Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials.Reportar como inadecuado

Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials. - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

* Corresponding author 1 Département de médecine générale 2 GICC - Génétique, Immunothérapie, Chimie et Cancer 3 Service de pharmacologie clinique Tours 4 LBBE - Laboratoire de Biométrie et Biologie Evolutive 5 CIC CHU Lyon inserm 6 Service de pharmacologie clinique

Abstract : BACKGROUND: The UK Prospective Diabetes Study showed that metformin decreases mortality compared to diet alone in overweight patients with type 2 diabetes mellitus. Since then, it has been the first-line treatment in overweight patients with type 2 diabetes. However, metformin-sulphonylurea bitherapy may increase mortality. METHODS AND FINDINGS: This meta-analysis of randomised controlled trials evaluated metformin efficacy in studies of metformin versus diet alone, versus placebo, and versus no treatment; metformin as an add-on therapy; and metformin withdrawal against cardiovascular morbidity or mortality in patients with type 2 diabetes. We searched Medline, Embase, and the Cochrane database. Primary end points were all-cause mortality and cardiovascular death. Secondary end points included all myocardial infarctions, all strokes, congestive heart failure, peripheral vascular disease, leg amputations, and microvascular complications. Thirteen randomised controlled trials 13,110 patients were retrieved; 9,560 patients were given metformin, and 3,550 patients were given conventional treatment or placebo. Metformin did not significantly affect the primary outcomes all-cause mortality, risk ratio RR = 0.99 95% CI: 0.75 to 1.31, and cardiovascular mortality, RR = 1.05 95% CI: 0.67 to 1.64. The secondary outcomes were also unaffected by metformin treatment: all myocardial infarctions, RR = 0.90 95% CI: 0.74 to 1.09; all strokes, RR = 0.76 95% CI: 0.51 to 1.14; heart failure, RR = 1.03 95% CI: 0.67 to 1.59; peripheral vascular disease, RR = 0.90 95% CI: 0.46 to 1.78; leg amputations, RR = 1.04 95% CI: 0.44 to 2.44; and microvascular complications, RR = 0.83 95% CI: 0.59 to 1.17. For all-cause mortality and cardiovascular mortality, there was significant heterogeneity when including the UK Prospective Diabetes Study subgroups I2 = 41% and 59%. There was significant interaction with sulphonylurea as a concomitant treatment for myocardial infarction p = 0.10 and 0.02, respectively. CONCLUSIONS: Although metformin is considered the gold standard, its benefit-risk ratio remains uncertain. We cannot exclude a 25% reduction or a 31% increase in all-cause mortality. We cannot exclude a 33% reduction or a 64% increase in cardiovascular mortality. Further studies are needed to clarify this situation.

Autor: Rémy Boussageon - Irène Supper - Theodora Bejan-Angoulvant - Nadir Kellou - Michel Cucherat - Jean-Pierre Boissel - Behrouz Kas



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