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*Data on smoking status were missing for 2 patients in the ENTYVIO group

The excess mortality reported in patients with CKD and high ALP levels has been controversially attributed to potential cardiovascular adverse effects as a result of very severe lack of control over bone-mineral metabolism.2,3,13,14 Several pathogenic mechanisms have been proposed to explain this association, including increased vascular calcification via pyrophosphate hydrolysis in the arterial wall,15 systemic inflammation16,17 and vitamin D deficiency.18 However, the absence of a significant association between serum levels of the bone-derived isoenzyme of ALP (bone-specific ALP) and mortality in patients with CKD19 raises serious doubts about the hypothesis on a pathogenic link with bone-mineral metabolism

J.AbeliovichH.Acevedo ArozenaA.et al (2016)

This review synthesizes current evidence on the molecular and cellular mechanisms underlying metformins glycemic control and cardiovascular benefits, highlighting both AMPK-dependent and AMPK-independent pathways

S.AndradeM