Scientists have made a breakthrough in understanding how metformin, a common medication taken by millions, works. The discovery could pave the way for other treatments after challenging previous assumptions.
Metformin is a prescription drug mainly used to treat type 2 diabetes, helping the body manage insulin and lower blood sugar levels. Until recently, experts believed it worked only in the liver and gut. However, a new study has found that the drug actually uses a previously unknown pathway in the brain to promote its anti-diabetic action.
Brain Pathway Discovery
Researchers at Baylor College of Medicine in America discovered that metformin activates SF1 neurons in the brain while simultaneously 'turning off' a protein called Rap1 in the ventromedial hypothalamus region. This protein affects how the body handles glucose, and the study found that metformin's ability to lower blood sugar relied on suppressing Rap1 activity.
Dr. Makoto Fukuda, associate professor of pediatrics-nutrition at Baylor College of Medicine, said, according to Science Daily: “We found that SF1 neurons are activated when metformin is introduced into the brain, suggesting they're directly involved in the drug's action. This discovery changes how we think about metformin. It's not just working in the liver or the gut, it's also acting in the brain. We found that while the liver and intestines need high concentrations of the drug to respond, the brain reacts to much lower levels.”
Implications for Treatment
Using genetically engineered diabetic mice, the researchers found that injecting metformin into the brain had a significant effect on blood sugar even when the dose was thousands of times lower than what would be taken orally. The researchers hope this discovery will unlock more precise treatments using this brain pathway and lift some of the mystery around metformin.
Millions of people worldwide rely on metformin to manage their blood sugar and insulin. While it is mostly prescribed for type 2 diabetics, it can also help those with gestational diabetes, prediabetes, and PMOS, previously known as polycystic ovarian syndrome. Unlike some other diabetes medications, metformin does not cause weight gain. However, it can cause side effects, according to the NHS, including nausea, vomiting, diarrhoea, stomach ache, loss of appetite, and a metallic taste in the mouth.
