It has been demonstrated in a mouse model of early diabetes using obese, insulin-resistant homozygous C57BL/6J-lepob (ob/ob−−) mice, that SGLT2is have been shown to cause metabolic changes in the form of an increase in plasma glucagon concentration and an increased glucagon/insulin ratio as well as an increase in the concentration of ketone bodies [71]. The gene discussed is INS; the disease is diabetes mellitus.