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Glucosuric, renal and hemodynamic effects of a dual inhibitor of SGLT1 and SGLT2, licogliflozin, in patients with chronic kidney disease: a randomized trial.

BACKGROUND
The beneficial effects of SGLT2 inhibitors in patients with chronic kidney disease (CKD) have been demonstrated. Whether inhibition of both SGLT1 and SGLT2 confers additional benefits is unknown. This study investigated the glucosuric, renal and hemodynamic effects of a dual SGLT1/2 inhibitor, licogliflozin, in patients with CKD.


METHODS
This multiple-dose, parallel-group, Phase II mechanistic study randomized 53 participants (18-78 years, body mass index ≤50kg/m2 ) with varying degrees of CKD or normal renal function to treatment with licogliflozin (50 mg q.d.) or placebo for 7 days. The study objectives were to assess the effects of licogliflozin on 24 h urinary glucose excretion (UGE24 ), renal function, hemodynamics, pharmacokinetics, and safety.


RESULTS
Licogliflozin treatment for 7 days significantly (p<0.01) increased UGE24 from baseline in participants with normal renal function (adjusted mean change: 41.8g [33.6, 49.9]) or with Mild (32.6g [24.1, 41.0]) or Moderate A (35.7g 28.6, 42.9]) or Moderate B (20.3 g 13.1, 27.5] CKD, but not in Severe (6.2 g [-0.71, 13.18]) CKD. Licogliflozin reduced urinary electrolytes (sodium, potassium and chloride), blood pressure (BP) and urinary volume to varying extent among different groups. Significant increases in renin (p<0.05), angiotensin II (p<0.05) and aldosterone (p<0.01) levels were observed. Adverse events (AEs) were generally mild, and most commonly included diarrhea (94%), flatulence (68%) and abdominal pain (21%).


CONCLUSION
Licogliflozin treatment results in significantly increased UGE and favorable changes in urinary electrolytes and hemodynamics in patients with varying degrees of CKD (eGFR≥45 mL/min/1.73 m2 ). This article is protected by copyright. All rights reserved.