Previous study has shown SGLT2 inhibitors affect tubule-glomerular feedback in macula densa associated with decreased glomerular filtration rate. Thereby, plasma renin activity(PRA) may acutely increase after treatment with SGLT2 inhibitors. However chronic activation of PRA-aldosterone system may introduce deterioration of atherosclerosis and fibrosis of heart muscle. The purpose of this study is to examine alterations of PRA and aldosterone concentration (PAC) after treatment with SGLT2 inhibitor in type 2 diabetic patients (T2D). We measured PRA and PAC in T2D (age 68±18 years old, men: female = 12:6) after treatment with SGLT2 inhibitors (tofogliflozin: 7 cases, empagliflozin: 6cases, canagliflozin: 3 cases) for 1 months and 6months (8 cases, age 63±16 years old, men: female = 7:1) from 2014 to 2017. Moreover, we could measured each metabolic parameters such as blood glucose, HbA1c, urinary Na/creatinine and blood pressure before and after treatment with SGLT2 inhibitors (SGLT2i) for 1month and 6months in T2D. We analyzed these results with paired t test using JMP12.2.0. SGLT2i significantly increased PRA for only 1month, but not PAC for 1 month and 6 months as follows; before PRA 1.9±2.4 ng/ml/h, 5.8±9.2 ng/ml/h for 1month (p<0.05) and 2.5±3.1 ng/ml/h for 6months, before PAC 104±65 pg/ml, 105±55 pg/ml for 1 month and 123±85 pg/ml for 6 months, respectively. Moreover, when we examined each metabolic parameter before and after treatment for 1 month, each body weight, BS, and HbA1c was significantly decreased (p<0.05). SGLT2i increases urinary sodium excretion, which affects macula densa in juxta-glomerular apparatus, and finally stimulates secretion of renin for 1month, but not for 6 months. The alteration of aldosterone were not observed after treatment with SGLT2 inhibitors for 1 and 6 months. These results suggest that SGLT2 inhibitors acutely affects PRA but not PAC, and chronic activation of PRA and PAC, which might cause cardiovascular events are not found.


I. Mori: None. T. Ishizuka: None.

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