THERAPEUTIC EFFECTS OF A SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR IN DIABETIC PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract

Objective: Multiple large-scale clinical trials have indicated that sodium glucose cotransporter 2 (SGLT2) inhibitors reduce the incidence of cardiovascular events, the deterioration of renal function and mortality. However, the therapeutic effects of SGLT2 inhibitors are supposed to be limited in patients with reduced renal function considering the mechanism of their action. Design and method: In this study, a SGLT2 inhibitor, ipragliflozin was given to 30 type 2 diabetic patients with nephropathy whose estimated glomerular filtration rate (eGFR) was not lower than 30 mL/min/1.73m2. The treatment was continued for 3 to 4 months and the effects on body weight, blood pressure (BP) and laboratory data including renal function, albuminuria and plasma B-type natriuretic peptide (BNP) were evaluated. Results: After 3 to 4 months, hemoglobin A1c was decreased by 0.6 % (p < 0.001), body weight was reduced by 1.8 kg (p < 0.01) and blood pressure was lowered by -10/-6 mmHg (p < 0.001/p < 0.001). This was accompanied by reductions in serum uric acid (-0.7 mg/dL, p < 0.001), triglycerides (-25 mg/dL, p = 0.028) and gamma-glutamyl transferase (-8 U/L, p = 0.001). On the other hand, plasma BNP was also decreased by 12 % (p = 0.020) and urinary albumin excretion was reduced by 23 % (p = 0.018) although the eGFR was not significantly changed. It is concluded that ipragliflozin is effective in lowering blood glucose even in patients with diabetic kidney disease and is beneficial in improving accompanying obesity and hypertension. In addition, ipragliflozin is thought to have favorable influences on the metabolisms of uric acid and lipids. Conclusions: These properties of ipragliflozin is expected to bring about protective effects against the progression of nephropathy and the development of cardiovascular disease resulting in the improvement of prognosis in diabetic patients with mild to moderate chronic kidney disease.