Ipragliflozin Improves Glycemic Control and Decreases Body Fat in Patients With Type 2 Diabetes Mellitus

Abstract

BackgroundIpragliflozin, a sodium-glucose transporter 2 inhibitor, was administered to patients with type 2 diabetes mellitus for 24 weeks to evaluate its effect on glycemic control and body composition.MethodsThis was an investigator-initiated multicenter prospective intervention study in which ipragliflozin (50 mg) was administered once daily and glycemic control, blood pressure, body weight (BW), body composition (measured by a biological impedance method), the lipid profile, and adverse events were evaluated after 4, 12, and 24 weeks of treatment.ResultsEfficacy and safety up to 24 weeks of ipragliflozin therapy were analyzed in 367 patients and 451 patients, respectively. Hemoglobin A1c decreased significantly from 8.07% at the start of ipragliflozin therapy to 7.26% in week 24 (P < 0.001). Fasting and postprandial blood glucose levels were significantly reduced by ipragliflozin. In week 24, there were significant decreases from baseline in BW (-2.6 kg), waist circumference (-2.9 cm), and body fat mass (-1.9 kg) (P < 0.001). The body water mass and mineral mass were decreased significantly by 0.5 and by 0.1 kg, respectively (P < 0.001), whereas the protein mass did not change significantly. Intracellular water mass did not change significantly, whereas extracellular water mass showed a significant decrease of 0.5 kg (P < 0.001). Muscle mass did not change in the upper and lower limbs, but that of the trunk decreased significantly (P < 0.001). There was a significant decrease in the fasting triglyceride level and a significant increase in fasting high-density lipoprotein cholesterol level, while low-density lipoprotein cholesterol was unchanged. Adverse events occurred in 23.5% of the patients, with a high frequency of genital infections, such as vulvovaginal candidiasis (3.1%) and genital pruritus (1.8%). Adverse drug reactions were noted in 13.7% of the patients.ConclusionsAdministration of ipragliflozin for 24 weeks improved glycemic control and decreased BW. Reduction of body fat accounted for more than 70% of the total weight loss and reduction of extracellular water accounted for about 20%.

Effect of ipragliflozin on liver function in Japanese type 2 diabetes mellitus patients: a subgroup analysis of the STELLA-LONG TERM study (3-month interim results)

“…These findings were comparable to the changes in AST, ALT, and γ-GTP levels (-2.4, -5.8, and -11.3 U/L, respectively) previously reported in a pooled analysis of five randomized controlled trials in patients treated with ipragliflozin [10]. Furthermore, the decrease in ALP (-8.9 U/L) observed in our study is in line with the findings of Kawata et al [24], who reported a -11.4 U/L change in ALP at 12 weeks after initiation of ipragliflozin therapy in the multicenter ASSIGN-K trial patient population. A clinically significant improvement in liver function parameters was only observed in the subgroup with abnormal liver function.…”

Ipragliflozin, a sodium–glucose cotransporter 2 inhibitor, reduces bodyweight and fat mass, but not muscle mass, in Japanese type 2 diabetes patients treated with insulin: A randomized clinical trial

“…Second, these measurements have rarely been included in randomized controlled trials. A single‐arm study with ipragliflozin showed a significant reduction in total muscle mass compared with baseline, as assessed with BIA. Third, the present patients were relatively older and leaner than those in previous studies.…”

“…In the present study, 80% of BW reduction resulted from fat mass reduction (Figure ). In the previous studies based on Japanese populations, 71–85% of BW reduction achieved with SGLT2 inhibitors resulted from fat loss as assessed with BIA, and the reduction rates seemed to be dependent on the “treatment period.” The studies showed a trend toward a greater reduction rate at 6 or 12 months than that at 3 months. That would be another reason for the minor difference in the fat reduction rate in the same population.…”

“…A single-arm study with ipragliflozin showed a significant reduction in total muscle mass compared with baseline, as assessed with BIA 15,24 . Third, the present patients were relatively older 15 and leaner than those in previous studies 4,[10][11][12][13]24 . Recent clinical trials showed the benefits of SGLT2 inhibitors for cardiovascular and renal outcomes, including heart failure 12,25 .…”

Long‐term (52‐week) efficacy and safety of ipragliflozin add‐on therapy to insulin in Japanese patients with type 1 diabetes mellitus: An uncontrolled, open‐label extension of a phase III study

“…The safety and efficacy of ipragliflozin in type 2 diabetes patients has been shown through clinical trials and post‐marketing surveys. Several studies have shown that ipragliflozin lowers blood glucose levels in an insulin‐independent fashion, and hence is expected to be efficacious in type 1 diabetes, as well as type 2 diabetes.…”