research letterIpragliflozin in combination with metformin for the treatment of Japanese patients with type 2 diabetes: ILLUMINATE, a randomized, double-blind, placebo-controlled study This multicenter, double-blind, placebo-controlled study examined the efficacy and safety of ipragliflozin, a sodium-glucose co-transporter 2 inhibitor, in combination with metformin in Japanese patients with type 2 diabetes mellitus (T2DM). Patients were randomized in a 2 : 1 ratio to 50 mg ipragliflozin (n = 112) or placebo (n = 56) once daily for 24 weeks, followed by a 28-week open-label extension in which all patients received 50 or 100 mg ipragliflozin, while continuing metformin. The primary outcome was the change in glycated haemoglobin (HbA1c) from baseline to week 24. HbA1c decreased significantly in the ipragliflozin group (−0.87%; adjusted mean difference from placebo: −1.30%; p < 0.001). The overall incidence of treatment-emergent adverse events was similar in both groups, although pollakiuria and constipation were more common in the ipragliflozin group; thus, ipragliflozin significantly improved glycaemic control and reduced body weight without major safety issues in Japanese patients with T2DM.

AimsTo assess the effects of renal impairment (RI) on the efficacy and safety of ipragliflozin in patients with type 2 diabetes mellitus (T2DM).MethodsA cohort of Japanese patients with T2DM and mild to moderate RI and poor glycaemic control, despite diet/exercise therapy alone or diet/exercise therapy in combination with an oral hypoglycaemic agent (an α‐glucosidase inhibitor, a sulfonylurea, or pioglitazone), were randomized in a double‐blind manner to 50 mg ipragliflozin or placebo once daily for 24 weeks. The patients continued open‐label ipragliflozin for a 28‐week extension period (total treatment duration: 52 weeks).ResultsIpragliflozin significantly decreased glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) levels and body weight from baseline to week 24 (last observation carried forward) compared with placebo in all patients with RI. The decreases in HbA1c and FPG levels were statistically significant in patients with mild RI, but not in patients with moderate RI. Ipragliflozin significantly reduced body weight in both RI groups. The improvements in glycaemic control were maintained in the 28‐week extension period. Ipragliflozin was associated with no clinically significant safety concerns, and its safety profiles were not influenced by the severity of RI.ConclusionsIpragliflozin significantly improved glycaemic control and body weight in patients with T2DM with mild RI, but did not improve glycaemic control in patients with moderate RI. Ipragliflozin is a valid treatment option for patients with mild RI but not those with moderate RI.

Aims/IntroductionIn the present dose–response study, we evaluated the efficacy and safety of ipragliflozin (ASP1941), a novel and selective inhibitor of sodium‐dependent glucose cotransporter 2, in Japanese patients with type 2 diabetes mellitus.Materials and MethodsA total of 361 patients from 39 Japanese centers were randomized to receive either once‐daily oral ipragliflozin (12.5, 25, 50 or 100 mg) or a placebo for 12 weeks.ResultsAll ipragliflozin‐treated groups had clinically significant, dose‐dependent decreases in glycated hemoglobin (HbA1c) and fasting plasma glucose levels compared with placebo‐treated groups. The adjusted mean difference in HbA1c change from baseline to the end of treatment between the placebo and 12.5, 25, 50, and 100 mg ipragliflozin groups were −0.61%, −0.97%, −1.29%, and −1.31%, respectively (P < 0.001). Reductions in HbA1c levels were similar between obese and non‐obese patients, and were larger in patients with baseline HbA1c ≥8.4% than in those with HbA1c <8.4%. Furthermore, bodyweight significantly (P < 0.001) and dose‐dependently decreased among ipragliflozin‐treated groups compared with the placebo group. The incidence of adverse events was similar across all groups. However, mild increases in hematocrit and blood urea nitrogen were found in ipragliflozin treated groups.ConclusionsOnce‐daily administration of ipragliflozin was dose‐dependently effective in glycemic control without major adverse effects. Ipragliflozin was equally effective between obese and non‐obese patients, and led to weight loss in both groups. Ipragliflozin was safe and well‐tolerated in Japanese patients with type 2 diabetes mellitus. This trial was registered with ClinicalTrials.gov (no. NCT00621868).

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Aims/IntroductionThe influence of overweight/obesity on the clinical efficacy and safety of sodium‐glucose co‐transporter 2 inhibitors is unclear. We carried out a pooled analysis to examine the impact of body mass index on the efficacy and safety of ipragliflozin.Materials and MethodsPatient‐level data were pooled for five Japanese double‐blind trials (NCT00621868, NCT01057628, NCT01135433, NCT01225081 and NCT01242215) in which patients were randomized to ipragliflozin or a placebo as monotherapy, or in combination with metformin, pioglitazone or a sulfonylurea. Outcomes included the changes in hemoglobin A1c, fasting plasma glucose, bodyweight and treatment‐emergent adverse events. Patients were divided into four body mass index categories.ResultsHemoglobin A1c, fasting plasma glucose and bodyweight decreased significantly in the ipragliflozin group compared with the placebo group in all body mass index categories, and in the total cohort (all P < 0.001). Hemoglobin A1c did not improve in 11.2 and 69.2% of patients in the ipragliflozin and placebo groups, respectively. The change in hemoglobin A1c was weakly correlated with the change in bodyweight in all patients (r = 0.136, P = 0.002). Regarding laboratory variables, the placebo‐subtracted difference tended to be greater in patients with higher body mass index for aspartate aminotransferase, alanine aminotransferase, γ‐glutamyl transpeptidase and uric acid. The incidences of treatment‐emergent adverse events were similar between the ipragliflozin and placebo groups in all patients combined and in the four body mass index categories.ConclusionsThese results show that the efficacy and safety of ipragliflozin are not influenced by obesity/overweight in Japanese patients.