Glucosuric, renal and haemodynamic effects of licogliflozin, a dual inhibitor of sodium‐glucose co‐transporter‐1 and sodium‐glucose co‐transporter‐2, in patients with chronic kidney disease: A randomized trial

Abstract Aim To investigate the glucosuric, renal and haemodynamic effects of licogliflozin, a dual sodium‐glucose co‐transporter‐1 and sodium‐glucose co‐transporter‐2 inhibitor, in patients with chronic kidney disease (CKD). Methods This multiple‐dose, parallel‐group, phase II mechanistic study randomized 53 participants (aged 18–78 years, body mass index ≤ 50 kg/m 2 ) with varying degrees of CKD or normal renal function to treatment with licogliflozin (50 mg once daily) or placebo for 7 days. The effects of licogliflozin on 24‐h urinary glucose excretion (UGE 24 ), renal function, haemodynamics, pharmacokinetics and safety were assessed. Results Licogliflozin treatment for 7 days significantly ( p < .01) increased UGE 24 from baseline in participants with normal renal function (adjusted mean change: 41.8 [33.6, 49.9] g) or with mild (32.6 [24.1, 41.0] g), moderate A (35.7 [28.6, 42.9] g) or moderate B (20.3 [13.1, 27.5] g) CKD, but not in severe (6.2 [−0.71, 13.18] g) CKD. Licogliflozin reduced urinary electrolytes (sodium, potassium and chloride), blood pressure and urinary volume to varying extents among different groups. Significant increases in renin ( p < .05), angiotensin II ( p < .05) and aldosterone ( p < .01) levels were observed. Adverse events were generally mild, and most commonly included diarrhoea (94%), flatulence (68%) and abdominal pain (21%). Conclusion Licogliflozin treatment results in significantly increased UGE and favourable changes in urinary electrolytes and haemodynamics in patients with varying degrees of CKD (estimated glomerular filtration rate ≥ 45 mL/min/1.73 m 2 ).