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‘No evidence’ metformin prevents cardiovascular disease

Although metformin is the ‘gold standard' treatment for diabetes, it has little effect on reducing the risk of death or cardiovascular disease, say the authors of two new analyses.

In findings that raise questions over the current treatment algorithm for managing diabetes, researchers also found metformin had no significant effects on common complications such as peripheral vascular disease, leg amputations and microvascular complications.

In one study they also said they could not exclude that metformin was associated with an increase in all-cause mortality of up to 53%.

NICE guidelines currently recommend metformin as first-line treatment for type 2 diabetes on the basis of its capacity to lower blood glucose, but these two new studies question whether its use to prevent the complications of diabetes is warranted.

In the first study, French researchers looked at 13 randomised controlled trials reporting cardiovascular outcomes, involving nearly 10,000 patients with diabetes on metformin.

Their meta-analysis found metformin did not significantly affect all-cause mortality or cardiovascular deaths, with only a 1% decrease in overall mortality and a 5% increase in cardiovascular mortality in those taking metformin, compared with those not taking the drug.

When analysing trials where metformin and sulphonylurea treatment was compared to sulphonylurea alone, inclusion of metformin was associated with a 53% increase in all-cause mortality and a 120% increase in cardiovascular deaths.

Rates of myocardial infarction, stroke, heart failure, peripheral vascular disease, leg amputations and microvascular complications also did not differ significantly between patients treated with metformin, and those who were not.

Another study, carried out by Danish researchers, analysed the results of 26 randomised trials comparing metformin and insulin treatment, versus insulin treatment alone.

They found no evidence of a reduced risk of death or cardiovascular mortality in patients treated with metformin and insulin, but there was reduced HbA1c levels, weight gain and insulin use in the metformin-treated group.

Study leader of the French study, Dr Remy Boussageon, lecturer at the Claude Bernard University in Lyon, said: ‘Surprisingly, this meta-analysis shows no evidence for benefits of metformin in terms of all-cause or mortality and all diabetes macro-vascular complications.

‘We cannot exclude beyond any reasonable doubt that use increases or decreases the risk of all-cause mortality or cardiovascular mortality.'

Professor Kamlesh Khunti, GP in Leicester and professor of primary care diabetes and vascular medicine at the University of Leicester, said it was hard to draw conclusions from the studies as most did not have long follow-ups or enough patients.

He said: ‘To get the benefits from you need to be on it for a long time, and recently there have been other benefits discovered with regard to cancer mortality.'

Risk ratios with metformin

All-cause mortality – 0.99

Cardiovascular deaths – 1.05

MI - 0.90

Heart failure – 1.03

Stroke – 0.76

PAD – 0.90

Leg amputations – 1.04

Microvascular complications -0.83

PLoS Medicine 2012, online 10 April


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