- Prescribing Advice for GPs - https://www.prescriber.org.uk -

Reappraisal of Metformin

PLoS Medicine has published the results of a meta-analysis that aimed to assess the efficacy of metformin in reducing all-cause and cardiovascular mortality in patients with type 2 diabetes.

The authors note that UKPDS 34 identified a significant risk reduction in all-cause mortality in overweight patients with type 2 diabetes when compared to dietary control alone. This same study reported an increased risk of mortality in non-overweight individuals who were treated with metformin and a sulphonylurea. This contrary finding, whilst still significant, has been largely ignored.

This analysis identified 13 randomised controlled trials involving 13,000 individuals. Around three quarters of these participants received metformin while the remainder received other treatments or a placebo. It was found that metformin had no effect on all-cause mortality (RR = 0.99; 95% CI 0.75 to 1.31) or cardiovascular mortality (RR = 1.05; 95% CI 0.67 to 1.64).

The authors note that the number and quality of studies available are insufficient to draw hard conclusions and that this study "cannot exclude a 25% reduction or a 31% increase in all-cause mortality". They conclude that "although metformin is considered the gold standard, its benefit/risk ratio remains uncertain". They also recognise that while further research is needed to help clarify the situation, metformin may not be the best comparator for newer hypoglycaemic drugs but remains unclear which comparator should be used.

Action: Clinicians should be aware of this analysis. While this study found metformin to have a neutral effect on mortality a significant benefit or harm could not be excluded. Pending further research, clinicians should continue to implement the current NICE Guideline for type 2 diabetes.