![]() The liver loses 80% of its metformin 4 h after the drug ingestion and eliminates 98% in 24 h. Bidirectional transport leads to metformin uptake and elimination at similar rates in the liver. Following oral administration of a therapeutic dose, metformin is mostly distributed in the gastrointestinal tract, liver, and kidney, and metformin concentrations are around 40–70 μM in the portal and reaches peak levels in the liver in 60 min ( Box 1). The maximum daily metformin dose prescribed to patients is 2.5 g. Fascinatingly, patients treated with metformin have reduced cancer incidence, and metformin increases the lifespan of C. In the USA, metformin was the fourth most prescribed drug in 2017 with 78.6 million prescriptions. After over 60 years of clinical use, metformin has proven to be safe and affordable, making it the most commonly prescribed oral anti-diabetic agent worldwide, taken by over 150 million people annually. The American Diabetes Association and the European Association for the Study of Diabetes officially recommended metformin as the initial drug for T2D in 2012. After 20 years of use in Europe, the Food and Drug Administration approved metformin to treat type 2 diabetes (T2D) in the USA in 1995. Jean Sterne, a physician scientist, conducted the first clinical trial on the use of metformin to treat diabetes and published his studies in 1957. Biguanides preserved the anti-diabetic effect of their parent compound with reduced toxicity, making them attractive treatment options. Several biguanides, including metformin, were synthesized in 1929. ![]() In 1918, guanidine was found to lower the blood glucose levels in rabbits, but it was too toxic for clinical use. In the late 1800s, this plant was determined to be rich in guanidine. In medieval times, the herb Gallega officinalis was used to treat patients with diabetes in Europe. ![]()
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