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Metformin is the first-line pharmacological treatment for type 2 diabetes. Worldwide, over 100 million patients are given this drug every year. Metformin was discovered before the advent of target-based drug discovery and its molecular action remains an area of vigorous diabetes research. The notion that 5' AMP-activated protein kinase (AMPK) mediates the anti-hyperglycaemic action of metformin has recently been challenged by genetic loss-of-function studies, thrusting AMPK-independent effects of the drug into the spotlight for the first time in more than a decade. A better understanding of metformin’s molecular targets is likely to enable target-based identification of second-generation drugs with similar properties, a development that has been impossible up to now. Towards this goal, the seminar will present recent research findings on metformin’s cellular action.