The diabetes drug metformin shows benefits for aging and a number of different diseases.
McMaster University researchers have uncovered one of the secrets behind metformin’s many benefits.
Metformin is one of the most widely used drugs in the world and is commonly prescribed for type 2 diabetes. In addition to its effects on lowering blood sugar, metformin shows benefits in preclinical models for aging and a number of different diseases including cognitive disorders, cancer, and cardiovascular disease.
One question researchers have asked is how this is achieved.
A multi-year study conducted by a collaboration of McMaster’s basic and clinical researchers found that metformin induces the expression and secretion of a protein called growth differentiation factor 15, or GDF15.
The results were published today (December 9, 2019) in Nature Metabolism.
“Studies over the past two decades have shown that metformin lowers more than just glucose, but we didn’t understand why,” said Gregory Steinberg, senior author and professor of medicine at McMaster. He is also co-director of the Metabolism, Obesity and Diabetes Research Center at McMaster.
“We started this study with the idea that metformin could communicate with other tissues in the body by causing the liver to secrete a protein. We were totally surprised to find out that metformin caused the secretion of GDF15, a protein known to suppress appetite. “
The study team took this knowledge and applied it to mice to better understand the science behind the result. Scientists deleted the gene that makes GDF15 in mice and then treated them with metformin. The results showed that mice without GDF15 did not eat less or lost weight despite administration of metformin, establishing GDF15 as the link between metformin and weight loss.
The researchers say the results open up a range of research opportunities. There are currently over 1,500 clinical trials registered to test metformin’s effects on aging and various diseases.
“The possibility that GDF15 may play a role in several beneficial effects of metformin treatment on aging or diseases such as cancer needs to be explored,” Steinberg said.
Reference: “Metformin-Induced Elevations in GDF15 Are Important to Appetite Suppression and Weight Loss Promotion” by Emily A. Day, Rebecca J. Ford, Brennan K. Smith, Pedrum Mohammadi-Shemirani, Marisa R. Morrow, Robert M. Gutgesell, Rachel Lu, Amogelang R. Raphenya, Mostafa Kabiri, Andrew G. McArthur, Natalia McInnes, Sibylle Hess, Guillaume Paré, Hertzel C. Gerstein and Gregory R. Steinberg, December 9, 2019, Nature Metabolism.
DOI: 10.1038 / s42255-019-0146-4
The study was funded by the Canadian Institutes for Health Research (CIHR) and Diabetes Canada.