Physicians have used the drug metformin to treat type 2 diabetes for more than half a century, but despite its prevalence, researchers have lacked a clear understanding of how it works.
In a new study from Yale University, researchers found the mechanism behind metformin and related type 2 diabetes drugs and debunked a previously held theory on how they work.
Studies in humans have shown that metformin inhibits the process of gluconeogenesis, which is how the liver makes glucose from non-glucose precursors such as amino acids and lactate.
How it accomplishes this, however, has been a mystery.
In the study, the team performed a series of experiments both in liver slices and in mice.
They were able to show that metformin, as well as the related drugs phenformin and galegine, could inhibit glycerol conversion to glucose.
It is not uncommon for drugs to be approved for clinical use despite researchers not understanding how they work if they are shown to be safe and effective.
But the team says research on poorly understood medications like metformin allows scientists to develop more beneficial treatments.
Taking metformin, for example, can lead to unpleasant side effects such as gastrointestinal distress, leading many patients to stop taking it.
The team hopes his team’s research can lead to the development of diabetes drugs with the safe efficacy of metformin but higher tolerability.
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The study is published in PNAS and was conducted by Gerald Shulman et al.
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