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Patients with indicators of high-risk or established ASCVD, chronic kidney disease, or heart failure According to the ADA, when considering an agent for add-on to metformin background therapy, the first recommended consideration is whether or not the patient has indicators of high-risk or established ASCVD, chronic kidney disease (CKD), or heart failure ( Figure 2 )

Indeed metformin showed synergic effects with Sorafenib (a multikinase inhibitor) (Kim et al., 2018a) and pioglitazone (a TDZ) (Kim et al., 2018a

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