By it had become the most popular metformin combination. A review of metformin overdoses reported to poison control centers over a five-year period found serious adverse events were rare, though the elderly appeared to be at greater risk. Among younger people with a higher body mass index , lifestyle modification was no more effective than metformin, and for older individuals with a lower body mass index, metformin was no better than placebo in preventing diabetes. Blake; Stanifer, John W. Multiple potential mechanisms of action have been proposed, including; inhibition of the mitochondrial respiratory chain complex I , activation of AMP-activated protein kinase AMPK , inhibition of glucagon-induced elevation of cyclic adenosine monophosphate cAMP with reduced activation of protein kinase A PKA , inhibition of mitochondrial glycerophosphate dehydrogenase , and an effect on gut microbiota. In , metformin, unlike some other similar compounds, was found not to decrease blood pressure and heart rate in animals.
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