To date, the molecular and pharmacological mechanisms underlying metformin’s ability to inhibit the TGF-β1 signaling pathway are unknown, and identifying these mechanisms represents an important challenge that may elucidate new molecular targets of metformin and promote target-based novel strategies against many diseases beyond diabetes in which TGF-β1 signaling malfunctions are indicated. The gene discussed is TGFB1; the disease is diabetes mellitus.