As diabetic nephropathy, the most common cause of kidney disease in hemodialysis patients, is associated with poor prognosis, prophylactic treatment to prevent its onset is important. Multiple recent reports describe studies of kidney protection in patients treated with a DPP-4 inhibitor or an SGLT2 inhibitor, but few reports have evaluated the long-term effect of treatment with both drugs. We thus investigated the hypoglycemic and kidney-protective effects of SGLT2 inhibitor administration in patients with type II diabetes mellitus receiving baseline treatment with a DPP-4 inhibitor. We enrolled 36 people with type II diabetes who had been receiving combined treatment for more than two years, as well as 45 people who had recently started taking an SGLT2 inhibitor after taking a DPP-4 inhibitor for more than six months between August 1, 2015, and March 31, 2020. These patients were divided into three groups according to renal function; group A: 30<eGFR≦60, group B: 60<eGFR≦90, and group C: 90< eGFR. We investigated HbA1c and the change in eGFR using an electronic medical chart retrospectively for two years from the time the combination was started. The subjects were 23 males and 13 females with an average age of 61 years old (range 28–83). An initial decrease in HbA1c level was found in all groups after combination therapy started. HbA1c levels in groups A and B decreased significantly after two years of treatment. eGFR decreased significantly in group C two years after beginning combination therapy with an SGLT2 inhibitor. In contrast, no significant decreases in eGFR or 1/Scr were observed in groups A or B. These findings suggest that long-term combination therapy with an SGLT2 inhibitor and a DPP-4 inhibitor in type II diabetes mellitus patients exerts hypoglycemic action and provides kidney protection.