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However, it is important to note a concluding sentence from Kulkarni et al.: These findings remain to be validated in other tissues and study designs and do not yet allow us to identify the primary site of action of metformin, which then may trigger the observed changes in gene expression (79)

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And, there is no excuse for prescribing spironolactone prior to heart failure because there is no peer-reviewed research showing that it would have any benefit to pre-CHF dogs

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