Millions of people take metformin, a Type 2 diabetes medication that lowers blood sugar. The “wonder drug” has also been shown to slow cancer growth, improve COVID outcomes and reduce inflammation. But until now, scientists have been unable to determine how, exactly, the drug works.
A new Northwestern Medicine study has provided direct evidence in mice that the drug reversibly cuts the cell’s energy supply by interfering with mitochondria, often referred to as the cell’s “powerhouse,” to lower glucose levels.
More specifically, metformin blocks a specific part of the cell’s energy-making machinery called mitochondrial complex I. In doing so, the drug can target cells that may be contributing to disease progression without causing significant harm to normal, healthy cells.
The study will be published Dec. 18 in the journal Science Advances.
“This research gives us a clearer understanding of how metformin works,” said corresponding author Navdeep Chandel, the David W. Cugell, MD, Professor of Medicine (Pulmonology and Critical Care), investigator with the Chan Zuckerberg Initiative and a professor of biochemistry and molecular genetics at Northwestern University Feinberg School of Medicine. The study’s first author is Colleen Reczek, research assistant professor of medicine (pulmonary and critical care medicine) at Feinberg.
This research significantly advances our understanding of metformin’s mechanism of action. While millions of people take metformin, understanding its exact mechanism has been a mystery. This study helps explain that metformin lowers blood sugar by interfering with mitochondria in cells.”
Navdeep Chandel, the David W. Cugell, MD, Professor of Medicine, Northwestern University