Insulin resistance and the brain: a diabetes medicine helped protect it
What was studied: Insulin resistance is when the body stops responding well to insulin, the hormone that moves sugar into cells. It is common and is a known risk factor for dementia. Researchers at the Mayo Clinic scanned the brains of 72 adults, with and without signs of insulin resistance, and tested their thinking skills. Then 40 older adults with insulin resistance were randomly given either metformin (a widely used diabetes medicine) or a placebo for 40 weeks, and the brain tests were repeated. They also ran an experiment in mice that lacked insulin signaling in the brain.
What they found: Older adults with insulin resistance had smaller brain volumes in areas important for memory and learning, including the hippocampus, and weaker connections between some brain areas. In the mice, brain cells made less energy and the animals did worse on memory tasks. In the trial, metformin improved the body's response to insulin, and helped keep brain sugar use, brain volume and brain connections steadier in certain areas involved in decision-making and learning. It was also linked to better scores on a combined measure of thinking speed and working memory.
Why it matters: This supports the idea at the heart of metabolic psychiatry: how well the body handles energy affects the brain. It suggests that some brain changes linked to insulin resistance may be preventable, not fixed.
Honest limits: The trial was small (40 people) and focused on older adults and dementia risk, not on mental illnesses such as depression or schizophrenia. Brain scans changing is not the same as people feeling or functioning better in daily life, and the thinking-skills result was modest. Part of the evidence comes from mice. We read the published summary, not the full paper.
Read the original: Pataky et al., "Metformin Preserves Regional Brain Glucose Uptake, Structure, and Functional Connectivity in Adults with Insulin Resistance," Journal of Clinical Investigation (2026). https://doi.org/10.1172/JCI207388 (PubMed summary: https://pubmed.ncbi.nlm.nih.gov/42944764/)
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