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Nine cats with measurable spontaneous cancer were treated with oral metformin for 14\u2009days. Monitoring included complete blood count (CBC), serum biochemistry, lactate,<jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content>, insulin\u2010like growth factor\u20101, and vascular endothelial growth factor serially until study completion. At the maximum tolerated dose of 10\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup>q12\u2009h side effects were primarily mild to moderate gastrointestinal upset (anorexia, vomiting, and\/or weight loss). All cats developed a reduction in haematocrit. Six of nine cats developed new or progressive hyperlactatemia and one cat developed asymptomatic lactic acidosis. There were no clinical responders and two cats had modest measurable reduction in tumour size. In conclusion, we demonstrate potential pharmacologic activity of metformin at a clinically relevant dose and identify parameters for clinical monitoring and supportive care. 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