For more than six decades, metformin has been one of the most widely used treatments for type 2 diabetes. However, scientists have never fully understood exactly how the drug helps control blood sugar levels.

Now, researchers from Baylor College of Medicine and international collaborators have uncovered a previously unknown role of the brain in metformin’s effects.

The study reveals that metformin works partly through a specific brain pathway that influences the body’s ability to regulate glucose. This discovery challenges the long-standing belief that the drug mainly acts through organs such as the liver and digestive system.

Metformin is commonly prescribed because it helps lower blood sugar, improves insulin sensitivity, and is generally considered safe and effective. Despite its widespread use, the biological mechanisms behind its action have remained a scientific mystery.

The newly identified brain pathway could help researchers develop more targeted diabetes treatments with improved effectiveness and fewer side effects.

Published in Science Advances, the research provides a deeper understanding of one of the world’s most important diabetes medicines and may open new possibilities for designing future therapies.

The findings also demonstrate that even well-established medicines can continue revealing new biological effects decades after they were first introduced.