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Integrative Health

After Decades Of Use, Metformin Is Found To Have A Surprising Effect On The Brain

Author: Molly Knudsen, M.S., RDN

March 28, 2026

Registered Dietitian Nutritionist

By Molly Knudsen, M.S., RDN

Registered Dietitian Nutritionist

Molly Knudsen, M.S., RDN is a Registered Dietician Nutritionist with a bachelor’s degree in nutrition from Texas Christian University and a master’s in nutrition interventions, communication, and behavior change from Tufts University. She lives in Newport Beach, California, and enjoys connecting people to the food they eat and how it influences health and wellbeing.

Image by Fly View Productions / iStock

March 28, 2026

Metformin has been the go-to medication for Type 2 diabetes for decades. It's affordable, effective, and has a strong safety track record.

But scientists are still uncovering exactly how it works. And some of its blood sugar-balancing impact may actually be linked to the brain.

What we thought we knew

For years, the understanding was that metformin works primarily by1 telling the liver to release less glucose into the bloodstream, improving insulin sensitivity, and helping slow intestinal glucose absorption. These mechanisms are well documented.

But the brain is becoming increasingly recognized as an organ in the blood sugar balancing equation. So researchers are now starting to investigate whether (and how) the brain contributes to metformin's effects in animals.

About the study

The most recent study2 on this was published in Science Advances in 2025 (and is just getting attention for its results). The researchers set out to examine whether the brain plays a role in metformin's glucose-lowering effects. Using mice, they investigated how different organs respond to varying concentrations of the drug. It's typical for studies investigating how a medication works in the body to start in mice or cell studies.

Its potential impact on the brain

The key finding? While the liver and intestines need high concentrations of metformin to respond, the brain reacts to much lower levels of the drug.

The findings suggest that even at typical doses, metformin may be working through brain pathways to help regulate blood sugar, a mechanism that wasn't fully appreciated until now.

Supporting research backs this up. A 2023 study3 found that when metformin is administered directly to the brain in mice, it activates the hypothalamus and works through both brain-gut and brain-liver pathways to regulate glucose. Another study4 showed that metformin increases levels of GDF15, a hormone that reduces food intake by acting on receptors in the brain stem.

This adds to a growing body of research showing that metformin's effects extend well beyond the liver, and that the brain is a key player in how the drug helps manage blood sugar.

Why the brain's role matters in blood sugar

The brain is increasingly recognized as a central regulator of whole-body metabolism. Yes, it controls hunger and satiety, but it also actively communicates with organs like the liver, gut, and pancreas to help maintain glucose balance.

This brain-body connection shows up across diabetes research. GLP-1s, for example, work in part by activating neurons in the hypothalamus5. But the brain's metabolic role goes beyond any single drug class.

Research suggests metformin may stimulate intestinal GLP-16 secretion, which then activates the gut-brain-liver axis to help regulate blood sugar. The hypothalamus, brain stem, and other regions all appear to play roles in sensing energy status and coordinating the body's response.

The fact that metformin (a medication that's been around since the 1950s) also appears to work through the brain underscores just how central this organ is to metabolic health. It's not just about what happens in your gut or liver.

What this means for you

If you're taking metformin, this doesn't change anything about how you take your medication. The medication works, and now we're learning more about why.

Rather, this research adds to our understanding of the brain's role in blood sugar regulation and metabolic health more broadly. It's a reminder that the body works as an interconnected system, and that science is still uncovering how even our most common medications do what they do.

The takeaway

Metformin played a key role diabetes treatment for decades, and this research suggests its effects may be more far-reaching than we realized. Even if you are taking blood sugar-regulating medication, adopting healthy lifestyle style is still crucial for long-term health. These five foods are great for blood sugar balance, and strength training (and the resulting muscle mass) also improve insulin sensitivity.

6 Sources

- https://www.ncbi.nlm.nih.gov/books/NBK518983/#:~:text=Mechanism%20of%20Action,to%20induce%20modest%20weight%20loss.

- https://www.science.org/doi/10.1126/sciadv.adu3700

- https://pubmed.ncbi.nlm.nih.gov/37153803/

- https://pubmed.ncbi.nlm.