Beneficial Effects of Ipragliflozin on the Renal Function and Serum Uric Acid Levels in Japanese Patients with Type 2 Diabetes: A Randomized, 12-week, Open-label, Active-controlled Trial

Abstract

Objective To examine the add-on effects, compared to the existing antidiabetes treatment, of the sodiumglucose cotransporter 2 inhibitor ipragliflozin on glycemic control and the risk factors of cardiovascular disease (CVD) and chronic kidney disease (CKD) in patients with inadequately controlled type 2 diabetes. Methods This 12-week, randomized, open-label, active-controlled trial included 30 patients with type 2 diabetes who were randomized 1:1 to ipragliflozin and control groups (n=15 each). The ipragliflozin group received 50 mg of ipragliflozin once daily in addition to conventional therapy. The primary outcome was the change in hemoglobin A1c (HbA1c) from the baseline. Secondary outcomes were changes from the baseline in indices of glycemic control, uric acid (UA), renal function, and arterial stiffness. Results The patients' diminished estimated glomerular filtration rate (eGFR) was alleviated in the ipragliflozin group compared to the control group [difference between groups (Δ)=4.6 (95% confidence interval (CI): 1.5-7.7) mL/min/1.73 m 2 , p=0.006] prior to significant improvements in HbA1c and other parameters, including anthropometric indices and arterial stiffness. Furthermore, ipragliflozin add-on therapy resulted in a greater reduction in serum UA levels than control therapy [Δ=-52.3 (95% CI:-85.5-19.1) μmol/L, p=0.003]. The changes in the eGFR with ipragliflozin treatment were associated with ipragliflozin-mediated changes in the UA, even after adjusting for the age, sex, baseline HbA1c, baseline UA, and baseline eGFR (standardized regression coefficient=-0.535, p=0.010). Conclusion Ipragliflozin add-on therapy was associated with beneficial renal effects in parallel with reducing serum UA levels.

Effects of sodium‐glucose cotransporter 2 inhibitors on serum uric acid in patients with type 2 diabetes mellitus: A systematic review and network meta‐analysis

“…After further screening, 19 RCTs with 39 arms fulfilled the inclusion criteria and were eventually included in the present study (Figure 1). These RCTs incorporated 4218 adult participants with T2DM, and six SGLT-2 inhibitors were included: empagliflozin, [25][26][27][28] dapagliflozin, [29][30][31][32][33] canagliflozin, 34 ipragliflozin, [35][36][37][38] luseogliflozin [39][40][41] and tofogliflozin. 42,43 In addition, the following baseline characteristics were extracted: registration number, study design, sample size, age, sex, treatment, control, study duration and baseline SUA levels (Table 1).…”

Factors associated with the uric acid‐lowering effects of sodium‐glucose cotransporter‐2 inhibition in patients with type 2 diabetes: Insights from the randomized PROTECT trial

“…A previous study of ipragliflozin in a randomized trial setting also reinforced the SUA-lowering effect in parallel with beneficial renal effects. 11 From a clinical point of view, it is important to identify specific patient populations most likely to achieve the benefit of SGLT2 inhibition in terms of reducing SUA levels. 12 Notably, subgroup analysis in this study indicated mildly impaired renal function and elevated SUA levels at baseline as factors associated with the greater uric acid-lowering effect.…”

Safety and effectiveness of ipragliflozin in Japanese patients with type 2 diabetes mellitus and impaired renal function: subgroup analysis of a 3-year post-marketing surveillance study (STELLA-LONG TERM)

“…Однако корреляция не означает причинно-следственную взаимосвязь; вот почему нельзя утверждать, что увеличение рСКФ на фоне лечения ипраглифлозином способствует снижению уровня мочевой кислоты сыворотки крови у пациентов с нарушением функции почек и ожирением. Тем не менее полученные результаты согласуются с данными предшествующего исследования ипраглифлозина, показавшего, что улучшение функции почек сопровождалось снижением уровня мочевой кислоты сыворотки крови [38].…”