ADA: Mortality Lower with Metformin

According to Ronan Roussel, MD, PhD, of Groupe Hospitalier Bichat-Claude Bernard in Paris, and colleagues, a large, multicenter trial found a 24% reduced risk of all-cause mortality among patients on the drug, compared with those not taking it.  

They presented their findings during a late-breaking session at the ADA meeting.

"In secondary prevention patients, the use of metformin was associated with a significant reduction in all-cause mortality after two years of follow-up," Roussel said. 

Previous studies, including the United Kingdom Prospective Diabetes Study (UKPDS) have suggested that metformin may carry a decreased risk of overall mortality. 

To explore the relationship, Roussel and colleagues assessed data from the Reduction of Atherosclerosis for Continued Health (REACH) registry, which enrolled more than 67,000 patients from 5,473 sites in 44 countries. Its purpose was to investigate risk factors for cardiovascular events in patients at risk of atherothrombotic disease and to assess the use of risk management strategies. 

In this analysis, Roussel and colleagues assessed the 19,699 patients over age 45 who had diabetes as well as documented cardiovascular disease or other atherothrombotic risk factors. Only 40% of the patients were treated with metformin at baseline, and they tended to be younger, heavier, and had better renal function. 

To take into account any of these potential confounding factors, the researchers used a propensity score, which included controlling for factors such as use of more cardioprotective drugs in patients on metformin. Over a two-year period, there were a total of 1,270 fatalities. 

The researchers found that patients on metformin had a significant 33% reduction in the risk of death compared with those not on the drug (95% CI 0.59 to 0.75, P<0.001). After adjustment with the propensity score, there was still a significant 24% reduction in death (95% CI 0.65 to 0.89, P<0.001). 

In additional analyses, Roussel said the protective effect may be more applicable to women, patients between 40 and 80, those with a history of heart failure, and concomitant use of insulin, but not all of these interactions were significant. 

Roussel concluded that the mortality finding "is consistent with the results of the UKPDS, with a Cochrane systematic review of trials of metformin as monotherapy, and with two other observational studies focusing on diabetic patients with congestive heart failure." He added that the data have broad applicability and should be explored in further trials. 

David M. Kendall, MD, of the University of Minnesota and the ADA's chief scientific & medical officer, stated that, "Certainly while the world is not looking for more reasons to use metformin ... this adds to the strength of the evidence that suggests a mortality benefit." 

Practice Pearls:

• Explain that patients with Type 2 diabetes taking metformin appeared to have a 24% lower risk of death from any cause than patients who weren't taking it.
• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal. 

Roussel R, et al "Metformin use and mortality among diabetic patients with established atherothrombosis" ADA 2010.