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Introduction Historically, the origins of metformin (dimethylbiguanide) came from the Middle Age where medieval doctors used extract from the French Lilac Galega officinalis to treat various diseases ( The Mitochondrial Respiratory-Chain Complex 1 as Primary Target of Metformin At the beginning of 2000, the group of Xavier Leverve was the first to report that metformin selectively inhibits the mitochondrial respiratory-chain complex 1 and, as a result, decreases NADH oxidation, reduces proton gradient across the inner mitochondrial membrane, and decreases oxygen consumption rate (Figure 1)