Reappraisal of Metformin Efficacy in the Treatment of Type 2 Diabetes: A Meta-Analysis of Randomised Controlled Trials

PLoS Medicine, 04/26/2012

Boussageon R et al. - Although metformin is considered the gold standard, its benefit/risk ratio remains uncertain. The authors cannot exclude a 25% reduction or a 31% increase in all-cause mortality. The authors cannot exclude a 33% reduction or a 64% increase in cardiovascular mortality.

Methods

  • 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.
  • The authors 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.

Results

  • 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 a significant interaction for myocardial infarction, p = 0.05.

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