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Metformin

Benefits of metformin go beyond for Type 2 diabetes

There are currently over 1,500 registered clinical trials to test the effects of metformin in aging and different diseases

Metformin, one of the most widely used medications in the world and is commonly prescribed for Type 2 diabetes, however in preclinical models, metformin also showed benefits on aging and a number of diverse diseases such as cognitive disorders, cancer and cardiovascular disease. Until now, the mechanisms were not fully understood, but researchers at McMaster University have unlocked one of the secrets behind the many benefits of metformin.

The multi-year study, ‘Metformin-induced increases in GDF15 are important for suppressing appetite and promoting weight loss’, published in Nature Metabolism, has found that metformin induces the expression and secretion of a protein called growth differentiating factor 15 (GDF15).

"Studies over the past two decades have shown that metformin does more than lower glucose, but we haven't understood why," said Gregory Steinberg, senior author and professor of medicine at McMaster. He is also co-director of the Centre for Metabolism, Obesity and Diabetes Research at McMaster. "We went into this study with the idea that metformin might communicate with other tissues in the body by causing the secretion of a protein from the liver. We were totally surprised when we found out that metformin caused the secretion of GDF15, a protein which is known to suppress appetite."

The study team took that knowledge and applied it to mice to better understand the science behind the outcome. Scientists deleted the gene that makes GDF15 in mice, then treated them with metformin. The results showed that mice without GDF15 did not eat less or lose weight, despite being administered metformin, establishing GDF15 as the connection between metformin and weight loss.

“Although further studies will be required to determine the tissue source(s) of GDF15 produced in response to metformin in vivo, our data indicate that the therapeutic benefits of metformin on appetite, body mass and serum insulin depend on GDF15,” the study concluded.

The researchers added the findings open a number of avenues of research. There are currently over 1,500 registered clinical trials to test the effects of metformin in aging and different diseases.

"The possibility that GDF15 has a role in multiple beneficial effects of metformin treatment on aging or diseases like cancer needs to be studied," said Steinberg.

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