Efficacy And Safety Of Ipragliflozin In Patients With Type 2 Diabetes: Assign-K Study

Background: Sodium glucose cotransporter 2 (SGLT2) inhibitors achieve good glycemic control in patients with type 2 diabetes, as well as reducing body weight and blood pressure. However, no large-scale clinical studies of SGLT2 inhibitors have been performed in Japan. The ASSIGN-K study investigated the efficacy and safety of ipraglitlozin, a selective SGLT2 inhibitor, in routine clinical practice.Methods: ASSIGN-K was an investigator-initiated, multicenter, prospective observational study of ipragliflozin that enrolled Japanese patients with type 2 diabetes who showed inadequate glycemic control despite diet and exercise with/without medication. Patients received ipragliflozin (50 mg/day) as monotherapy or combined with other antidiabetic agents for up to 104 weeks.Results: In 301 patients who completed104 weeks of ipragliflozin treatment, hemoglobin A1c was significantly reduced from 8.07% at baseline to 7.24% (P < 0.001), while fasting blood glucose (n = 86) and postprandial blood glucose (n = 75) were decreased significantly by 19.8 mg/dL (P < 0.001) and 29.6 mg/dL (P < 0.05), respectively. Body weight (n = 217) also showed a significant decrease from 79.1 kg to 76.2 kg (P < 0.001). In addition, body fat (n = 217) and fat-free mass (n = 217) were significantly reduced by 1.87 kg and 1.02 kg. respectively (both P < 0.001), while total body water displayed a significant decrease of 0.74 kg (P < 0.001). Similar results were obtained when 30 patients aged >= 65 years were compared with 187 patients aged < 65 years. Multiple regression analysis revealed greater improvement of hemoglobin A1c when the baseline value was higher, while improvement became less marked as the duration of diabetes became longer and as the baseline body mass index increased. In patients achieving hemoglobin A1c < 7.0%, baseline hemoglobin Alc was significantly lower than in patients not achieving hemoglobin A1c < 7.0%, (7.45% vs. 8.54%, P < 0.001) and the duration of diabetes was significantly shorter (8.66 vs. 10.69 years, P= 0.002). Ketoacidosis was only reported in patients who continued ipragliflozin treatment during intercurrent illness.Conclusions: In patients with type 2 diabetes and inadequate glycemic control, ipragliflozin significantly improved hemoglobin A1c regardless of baseline characteristics, including age, sex, hemoglobin A1c, and body mass index. However, it is important to suspend treatment with ipragliflozin during intercurrent illness.