Obesity is increasingly associated with the transformation of monoclonal gammopathy of undetermined significance (MGUS) into multiple myeloma (MM). Obesity, MGUS, and MM share common etiopathogenesis mechanisms including altered insulin axis and the action of inflammatory cytokines. Consistent with this interconnection, metformin could predominantly exert inhibition of these pathophysiological factors and thus be an attractive therapeutic option for MGUS. Despite the possible clinical significance, only a limited number of epidemiological studies have focused on obesity as a risk factor for MGUS and MM. (is review describes multiple biological pathways modulated by metformin at the cellular level and their possible impacts on the biology of MGUS and its progression into MM.