Improved cardiometabolic risk factors in Japanese patients with type 2 diabetes treated with ipragliflozin: a pooled analysis of six randomized, placebo-controlled trials

Abstract

To examine differential improvements among cardiovascular risk factors in response to treatment with ipragliflozin in Japanese type 2 diabetes mellitus (T2DM) patients, we conducted a pooled analysis of six randomized, double-blind trials of Japanese T2DM patients who received ipragliflozin 50 mg/day or placebo and had patient-level data for cardiometabolic risk parameters. Risk factors included glycated hemoglobin (HbA1c), body weight, homeostatic model assessment for insulin resistance and beta-cell function (HOMA-R and HOMA-beta, respectively), systolic blood pressure, fasting serum insulin concentrations, and the concentration of uric acid, lipids, and liver enzymes from baseline to end of treatment (EOT; 12-24 weeks). The primary endpoint of each trial was the change in HbA1c from baseline to EOT. Changes in risk factors from baseline to EOT were compared between ipragliflozin-treated and placebo groups, and between two subgroups (high- and low-risk groups for each parameter). All parameters, except low-density lipoprotein cholesterol (LDL-C) and non high-density lipoprotein cholesterol (non HDL-C), improved significantly in the ipragliflozin group. Subgroup analysis revealed a significantly greater improvement in the high-risk group versus low-risk group in HbA1c, HOMA-R, HOMA-beta, aspartate transaminase, alanine transaminase, and gamma-glutamyltransferase, but not in any of the lipid parameters or blood pressure. Liver function improvement in the ipragliflozin group was significantly correlated with changes in body weight, HbA1c, HOMA-beta, and HOMA-R. This analysis demonstrated that, in Japanese T2DM patients, ipragliflozin 50 mg/day was associated with improvements in cardiometabolic risk factors, except for LDL-C and non HDL-C.

Real-World Evidence for Long-Term Safety and Effectiveness of Ipragliflozin in Japanese Patients with Type 2 Diabetes Mellitus: final Results of a 3-Year Post-Marketing Surveillance Study (STELLA-LONG TERM)

“…In a preliminary randomized, parallelgroup study of Japanese patients with T2DM, patients treated with ipragliflozin experienced a statistically significant reduction from baseline in small dense LDL-C levels and an increase in LDL particle size [52]. In contrast, in a pooled analysis of six randomized, double-blind trials of ipragliflozin, no improvement in LDL-C or non HDL-C levels was found despite improvements in other cardiometabolic risk factors [53]. The results of the present study provide further, real-world, support for improvements in lipid parameters with long-term ipragliflozin therapy.…”

Safety of Ipragliflozin in Patients with Type 2 Diabetes Mellitus: Pooled Analysis of Phase II/III/IV Clinical Trials

“…In addition to improved glycaemic control [5–16], SGLT2 inhibitors provide important clinical benefits for patients with T2DM. Unlike most other anti-hyperglycaemic agents, SGLT2 inhibitors promote weight loss [15, 17], lower blood pressure [18–21] and exert beneficial effects on other cardiometabolic risk factors, except for low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol [22]. Indeed, patients with T2DM at high risk for cardiovascular (CV) events have been shown to have a lower incidence of CV outcomes and death after treatment with SGLT2 inhibitors [23–27].…”

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

“…Furthermore, the EMPA-REG OUTCOME trial (8,9) and the CANVAS program (14,15) reported that the beneficial effects of SGLT2 inhibitors on the eGFR occurred concomitantly with glycemic improvements. The reduction in the UA levels was also observed concurrently with the improvement in the glucose metabolism following SGLT2 inhibitor administration (28)(29)(30)(31)(32). These results suggest that the renal benefits of SGLT2 inhibitors are involved in the changes in several parameters, including UA levels and glucose metabolism.…”