Metformin for All?

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Since its United States debut in 1995, metformin has overcome initial doubts about its safety to become the recommended first-line drug for Type 2 diabetes, and the most widely prescribed diabetes drug in the world. This massive increase in popularity has been fueled by numerous studies on the drug, which have shown that it may have benefits ranging from weight loss to a lower risk of developing cancer. But some doctors, while generally supportive of the drug as an option for treating Type 2 diabetes, have felt that metformin’s best-for-everyone reputation is not supported by the evidence currently available.

A public debate about the merits of metformin took place earlier this year at the European Association for the Study of Diabetes (EASD) 2014 Meeting in Vienna. As noted in a Medscape article summarizing the debate, the lead skeptic of metformin’s position as the drug of choice for everyone with Type 2 diabetes was Rury Holman, MD, director of the University of Oxford Diabetes Trials Unit in the United Kingdom. Arguing in favor of metformin’s first-line position was Harold Lebovitz, MD, professor of medicine at the State University of New York Health Center in Brooklyn, New York. In support of metformin, Lebovitz argues that even though the well regarded UK Prospective Diabetes Study (UKPDS) found metformin to be no more effective at lowering HbA1c than other drugs (including sulfonylureas and insulin), it was found to be statistically significant in reducing diabetes-related deaths.

Lebovitz conceded, however, that since UKPDS there have been no good randomized controlled trials (considered the “gold standard” for medical evidence) of metformin. And one study, known as HOME, found no difference in cardiovascular outcomes between metformin and a placebo (inactive pill). But most studies of metformin have been observational, meaning that they follow people already taking certain drugs rather than assigning participants to take one drug or another. This type of study always leaves the possibility that any outcome might not be the result of taking a particular drug, but instead of some factor that led to that drug being prescribed in the first place. As a hypothetical example, if doctors prescribing metformin tended to be better informed than those prescribing other drugs, then better outcomes in patients taking metformin might be the result of better diabetes care in other ways, rather than the drug they were prescribed.

And while both doctors agreed on the limits of drawing conclusions from observational studies, Lebovitz noted that a large number have found benefits in longevity and cardiovascular health associated with metformin. Holman, on the other hand, noted that the small risk of lactic acidosis associated with metformin is still a drawback because of the danger posed by that condition, and that only one small clinical trial, UKPDS, has found a cardiovascular benefit from metformin. In addition, a meta-analysis (combination study) of several clinical trials found no effect on cancer risk from taking metformin. Holman concluded that more clinical trials of metformin are needed to confirm that the benefits found in observational studies are, in fact, real.

Do you take metformin? If so, do you care about potentially beneficial side effects like a lower risk of cardiovascular disease or cancer, or would you stick with the drug just for its effect on blood glucose? Should the government fund a long-term clinical trial of metformin? If you take a different diabetes drug, are you worried that you’re missing out on the benefits attributed to metformin? Leave a comment below!

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