Biguanides

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Metformin (Glucophage), currently the only biguanide, acts by reducing hepatic glucose production and increasing insulin sensitivity in muscle and fat cells. The liver normally releases glucose by detecting the level of circulating insulin. When insulin levels are high, glucose is available in the blood, and the liver produces little or no glucose. When insulin levels are low, there is little circulating glucose, so the liver produces more glucose. In type 2 diabetes, the liver may not detect levels of glucose in the blood and, instead of regulating glucose production, releases glucose despite blood sugar levels.

Metformin sensitizes the liver to circulating insulin levels and reduces hepatic glucose production.

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