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Patients with a dual therapy with metformin and a DPP-4 inhibitor can also receive a further treatment intensification with a SGLT-2 inhibitor or a TZD (7074)

Thus, Kim et al

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Within inflamed adipose tissue, key insulin receptor signaling intermediates are disrupted: insulin receptor substrate 1 (IRS-1) becomes serine-phosphorylated, and glucose transporter type-4 (GLUT4) expression and translocation are reduced, collectively impairing insulin-mediated glucose uptake and potentiating systemic insulin resistance [17]