Safety and efficacy of tofogliflozin in Japanese patients with type 2 diabetes mellitus in real‐world clinical practice: Results of 3‐month interim analysis of a long‐term post‐marketing surveillance study (J‐STEP/LT)

Abstract

Aims/Introduction The present study analysis was carried out to evaluate the safety and efficacy of tofogliflozin, a sodium–glucose cotransporter 2 inhibitor, in Japanese patients with type 2 diabetes mellitus in real‐world clinical practice. Materials and Methods This was a 3‐year non‐interventional observational study of patients with type 2 diabetes mellitus newly administered tofogliflozin who were uncontrolled on current therapy. We carried out a 12‐week interim analysis of tofogliflozin as part of 3‐year post‐marketing surveillance study. The incidence of adverse drug reactions was evaluated as a safety end‐point. As efficacy end‐points, glycated hemoglobin and bodyweight were evaluated. Results A total of 6,897 patients were enrolled. Tofogliflozin significantly reduced mean changes from baseline glycated hemoglobin (−0.63%, P < 0.0001) and bodyweight (−2.02 kg, P < 0.0001). The change in glycated hemoglobin and bodyweight reductions in response to tofogliflozin was consistently observed in all body mass index subgroups. Adverse drug reactions occurred in 345 of 6,712 patients (5.14%). There was a low incidence of adverse drug reactions known to be associated with sodium–glucose cotransporter 2 inhibitors, and they were reported as non‐serious. The incidences of polyuria/pollakiuria were higher in patients aged ≥65 years than <65 years, and were significantly different among estimated glomerular filtration rate subgroups. Urinary tract and genital infections occurred more frequently in women than in men. Conclusions Tofogliflozin was well tolerated, and no emerging new safety concerns were observed. Tofogliflozin significantly improved glycemic control with no impact on bodyweight gain. The short‐term administration of tofogliflozin is considered to have a favorable benefit–risk profile in Japanese patients with type 2 diabetes mellitus.

Safety and effectiveness of tofogliflozin in Japanese patients with type 2 diabetes mellitus: Results of 24‐month interim analysis of a long‐term post‐marketing study (J‐STEP/LT)

“…Regarding hypoglycemia, four cases were severe; one patient was treated with tofogliflozin and insulin product, and the other three patients received dipeptidyl peptidase‐4 inhibitors, sulfonylureas, thiazolidinedione and/or α‐glycosidase inhibitors as a concomitant antidiabetic. These severe hypoglycemia occurred within the first year, with onset on day 6, 16, 285 and 305 after the start of administration of tofogliflozin, as reported in the previous report of the 12‐month analysis, but not reported during the observation period from 12 to 24 months. As observed in the present study, polyuria/pollakiuria and volume depletion‐related events are often caused by SGLT2 inhibitors as a class effect due to their mild osmotic diuretic activity.…”

“…This report presents the results of the 104‐week interim analysis of a 3‐year post‐marketing study of tofogliflozin in patients with type 2 diabetes mellitus to evaluate the safety and effectiveness of tofogliflozin (J‐STEP/LT study). The tolerability, safety and effectiveness of tofogliflozin were maintained at 104‐week treatment, and the results were compared favorably along with the findings from the 3‐month and 12‐month interim analyses.…”

“…The details of the present study have been reported elsewhere. In brief, this Japanese Study of Tofogliflozin with Type 2 Diabetes Mellitus Patients in an Observational/Long‐Term (J‐STEP/LT) was a prospective, observational and multicenter post‐marketing study co‐sponsored by the manufacturers to evaluate the safety and effectiveness of two tofogliflozin hydrate products, Deberza ® 20‐mg tablet (Kowa Company, Ltd., Nagoya, Japan) and Apleway ® 20‐mg tablet (Sanofi K.K., Tokyo, Japan).…”

“…We, therefore, designed a 3‐year post‐marketing study of tofogliflozin in patients with type 2 diabetes mellitus to evaluate the safety and effectiveness in routine clinical practice. The 3‐month and 12‐month interim analyses showed that tofogliflozin was well‐tolerated, safe and clinically effective. Here, we report the 24‐month results of the interim analysis.…”

Effects of ipragliflozin on the development and progression of kidney disease in patients with type 2 diabetes: An analysis from a multicenter prospective intervention study

“…Although there was a difference in the amount of change, there were no significant differences in the measured values between groups, and as tests within the group also showed a significant decrease at most time points, eGFR at the starting point is not believed to have an effect. This point has been reported in studies of tofogliflozin 31 , and has been reproduced here in this study of ipragliflozin. Stratification analysis of eGFR at the starting point in patients treated with canagliflozin showed HbA1c decreases were larger in groups with high eGFR at the starting point, but HbA1c levels at the starting point were almost the same at 8.2-8.3 32 .…”