Ipragliflozin Add-on Therapy to a GLP-1 Receptor Agonist in Japanese Patients with Type 2 Diabetes (AGATE): A 52-Week Open-Label Study

Hisamitsu Ishihara, Susumu Yamaguchi, Ikko Nakao, Taishi Sakatani, Hisamitsu Ishihara, Susumu Yamaguchi, Ikko Nakao, Taishi Sakatani

Abstract

Introduction: Few data are available regarding ipragliflozin treatment in combination with glucagon-like peptide-1 (GLP-1) receptor agonists. The aim of this study was to evaluate the efficacy and safety of ipragliflozin in combination with GLP-1 receptor agonists in Japanese patients with inadequately controlled type 2 diabetes mellitus (T2DM).

Methods: This multicenter study (consisting of three periods: a 4-week washout period, a 6-week observation period, and a 52-week open-label treatment period) included patients aged ≥ 20 years who received a stable dose/regimen of a GLP-1 receptor agonist either solely or in combination therapy with a sulfonylurea for ≥ 6 weeks, with glycosylated hemoglobin (HbA1c) of ≥ 7.5% and a fasting plasma glucose (FPG) of ≥ 126 mg/dL. Ipragliflozin treatment was given at a fixed dose of 50 mg/day for 20 weeks, followed by 50 or 100 mg/day for 32 weeks. Changes from baseline in glycemic control and other parameters were examined; safety was also assessed.

Results: The mean changes in HbA1c and body weight from baseline to end of treatment were - 0.92% and - 2.69 kg, respectively, in all ipragliflozin-treated patients (n = 103). Overall, sustained reductions from baseline were observed for HbA1c, FPG, self-monitored blood glucose, and body weight during the 52-week treatment. The dose increase of ipragliflozin to 100 mg/day resulted in better glycemic control and weight reduction for patients in whom the 50-mg dose was insufficient. Overall, 46.6% (48/103) of patients experienced drug-related adverse events. The most common drug-related treatment-emergent adverse events were pollakiuria (9.7%), hypoglycemia (8.7%), constipation (6.8%), and thirst (5.8%).

Conclusion: Combined therapy with ipragliflozin and GLP-1 receptor agonists/sulfonylureas was significantly efficacious in reducing glycemic parameters in patients with T2DM with inadequate glycemic control, and no major safety concerns were identified. The results from this study suggest that ipragliflozin can be recommended as a well-tolerated and effective add-on therapy to a GLP-1 receptor agonist for the treatment of T2DM.

Trial registration: ClinicalTrials.gov (identifier: NCT02291874).

Funding: Astellas Pharma Inc., Tokyo, Japan.

Keywords: Diabetes mellitus, type 2; Glucagon-like peptide-1 receptor; Ipragliflozin; Sodium-glucose cotransporter 2.

Figures

Fig. 1
Fig. 1
Study design. GLP-1RA Glucagon-like peptide-1 receptor agonist, IPRA ipragliflozin, SU sulfonylurea
Fig. 2
Fig. 2
Flow chart of patient disposition during the study
Fig. 3
Fig. 3
a Time course of glycosylated hemoglobin (HbA1c) of patients in each dose subgroup, b time course of changes in HbA1c from baseline to end of treatment of patients in each dose subgroup. Data are shown as the mean and standard deviation (SD) (full analysis set) for all patients who received ipragliflozin. Error bars: SD. The number of patients at each time point is shown below the x-axis. EOT End of the treatment period, LOCF last observation carried forward
Fig. 4
Fig. 4
a Time course of fasting plasma glucose (FPG) of patients in each dose subgroup, b time course of changes in FPG from baseline to end of treatment of patients in each dose subgroup. Data are shown as the mean and SD (full analysis set) for all patients who received ipragliflozin. Error bars: SD. The number of patients at each time point is shown below the x-axis
Fig. 5
Fig. 5
Seven-point self-monitored blood glucose (SMBG) profile at baseline and EOT in each dose subgroup. Error bars: SD
Fig. 6
Fig. 6
Changes in seven-point SMBG profile from baseline to end of treatment in each dose subgroup. Error bars: SD
Fig. 7
Fig. 7
a Time course of body weight of patients in each dose subgroup, b time course of changes in body weight from baseline to end of treatment of patients in each dose subgroup. Data are shown as the mean and SD (full analysis set) for all patients who received ipragliflozin. Error bars: SD. The number of patients at each time point is shown below the x-axis

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Source: PubMed

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