INS and type 2 diabetes mellitus: Metformin was shown to reduce the risk of cancer development in T2DM via several indirect mechanisms: (1) reducing circulatory androgens, (2) inducing hepatic adenosine monophosphate kinase phosphorylation, (3) lowering blood glucose and gluconeogenesis, (4) reducing insulin level, and (5) exerting anti-inflammatory effects [130,131].