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#270 ‒ Journal club with Andrew Huberman: metformin as a geroprotective drug, the power of belief, and how to read scientific papers

The Peter Attia Drive

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Metformin: Mechanism of Action and Impact on Glucose Output

Metformin, a long-standing drug for type 2 diabetes, operates primarily by inhibiting the first complex of the mitochondrial electron transport chain, which plays a critical role in ATP production. Unlike lethal substances like cyanide, which completely block energy production, metformin acts as a weak inhibitor, reducing the overall efficiency of glucose metabolism. This inhibition alters the balance between adenosine monophosphate (AMP) and adenosine diphosphate (ADP), leading to decreased hepatic glucose production. This reduction is crucial for managing blood glucose levels, as the liver’s ability to regulate glucose output directly impacts metabolic health. Notably, while normal blood sugar levels are maintained with just about 5 grams of glucose in circulation, excessive liver glucose output is a key characteristic of type 2 diabetes, highlighting metformin's therapeutic role in this condition.

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