Safety and effectiveness of tofogliflozin in Japanese patients with type 2 diabetes mellitus treated in real‐world clinical practice: Results of a 36‐month post‐marketing surveillance study (J‐STEP/LT)

Abstract

Aims/Introduction Tofogliflozin is a sodium–glucose cotransporter 2 (SGLT2) inhibitor that lowers plasma glucose levels by enhancing urinary glucose excretion. After its approval in Japan in 2014 for the treatment of type 2 diabetes mellitus, we carried out a 3‐year prospective observational post‐marketing surveillance study in Japanese patients (Japanese Study of Tofogliflozin with Type 2 Diabetes Mellitus Patients/Long Term [J‐STEP/LT]). Materials and Methods This surveillance was carried out between September 2014 and February 2019, and recorded safety in terms of adverse drug reactions (ADRs) and ADRs of special interest, and effectiveness in terms of changes in glycated hemoglobin and bodyweight from baseline to last observation carried forward. Results Of 6,897 patients with type 2 diabetes mellitus registered, 6,711 and 6,451 were analyzed for safety and effectiveness, respectively. ADRs were reported in 846 patients (12.61%), with serious ADRs in 101 patients (1.5%). ADRs of special interest included hypoglycemia (62 patients [0.9%]), polyuria/pollakiuria (90 [1.3%]), volume depletion‐related disorders (135 [2.0%]), urinary tract infections (91 [1.4%]), genital infections (117 [1.7%]) and skin diseases (53 [0.8%]). One case of diabetic ketoacidosis was reported. The mean ± standard deviation changes from baseline to last observation carried forward in glycated hemoglobin and bodyweight were −0.68 ± 1.34% (n = 6,158, P < 0.0001) and −3.13 ± 4.67 kg (n = 5,213, P < 0.0001), respectively. Conclusions J‐STEP/LT, a 3‐year, prospective, observational, post‐marketing study in Japan, found no unprecedented ADRs, and consistent reductions from baseline in glycated hemoglobin and bodyweight over the observation period. The present results provide further evidence regarding the safety and tolerability of tofogliflozin in Japanese patients with type 2 diabetes mellitus.

Changes in the estimated glomerular filtration rate and predictors of the renal prognosis in Japanese patients with type 2 diabetes: A retrospective study during the 12 months after the initiation of tofogliflozin

“…Similar to post-marketing surveillances [ 23 – 25 ], the reduction in HbA1c after starting tofogliflozin in the low-eGFR group was inferior to that in the normal-eGFR group. On the other hand, body weight, systolic blood pressure, uPE, uACR, urinary L-FABP, and serum uric acid decreased, and hemoglobin increased in the low-eGFR group.…”

“…The frequencies of overall and individual AEs were not markedly different between the normal- and low-eGFR groups in the present study, although AEs associated with SGLT2 inhibitor use are generally more frequently observed in subjects with renal dysfunction than in those without it [ 11 , 23 – 25 , 47 ]. The prescription of tofogliflozin in this study was performed more than five years after SGLT2 inhibitors were first launched in Japan.…”

Real-World Safety and Effectiveness of Canagliflozin Treatment for Type 2 Diabetes Mellitus in Japan: SAPPHIRE, a Long-Term, Large-Scale Post-Marketing Surveillance

“…Regarding the safety of canagliflozin, the types of ADRs reported in this surveillance were also recorded in the clinical trial program [2] and were generally similar to those reported for other SGLT2 inhibitors [18][19][20][21]. Most of the ADRs with an incidence of C 0.1% have already been listed in the package insert for canagliflozin [1].…”

Comparative safety of different sodium-glucose transporter 2 inhibitors in patients with type 2 diabetes: a systematic review and network meta-analysis of randomized controlled trials

“…A Korean post-marketing surveillance study of empagliflozin (10 and 25 mg) revealed that the most common adverse event was pollakiuria, with incidence rates of 0.59% ( 123 ). A Japanese post-marketing surveillance study of 100 mg of canagliflozin showed that the most common adverse event was pollakiuria, with an incidence rate of 0.79% ( 124 ). A 36-month post-marketing surveillance study found that the pollakiuria incidence rate of tofogliflozin was 1.3% in Japanese patients ( 125 ).…”