Safety and effectiveness of tofogliflozin in elderly Japanese patients with type 2 diabetes mellitus: A post‐marketing study (J‐STEP/EL Study)

Abstract

Aims/IntroductionAlthough sodium‐glucose cotransporter 2 inhibitors are a promising treatment for type 2 diabetes mellitus, they are associated with concerns about specific adverse drug reactions. We carried out a 1‐year post‐marketing study of tofogliflozin, a novel agent in this class, in Japanese elderly patients with type 2 diabetes mellitus.Materials and MethodsThis was a prospective, observational and multicenter post‐marketing study carried out in the context of routine clinical practice. The study included all type 2 diabetes patients aged ≥65 years who started treatment with tofogliflozin during the first 3 months after its launch on 23 May 2014.ResultsOf 1,535 patients registered, 1,507 patients whose electronic case report forms were collected and who had at least one follow‐up visit were included in the safety analysis. A total of 270 of 1,507 patients (17.92%) had at least one adverse drug reaction to tofogliflozin. The incidences of adverse drug reactions of special interest, namely, polyuria/pollakiuria, volume depletion‐related events, urinary tract infection, genital infection, hypoglycemia and skin disorders were 2.92, 3.85, 2.06, 1.33, 1.06 and 2.39%, respectively. Among those patients evaluable for clinical effectiveness, the mean change in glycated hemoglobin and bodyweight from baseline to last visit was −0.46% (P < 0.0001) and −2.71 kg (P < 0.0001), respectively.ConclusionsThe present study showed that the incidence of adverse drug reactions to tofogliflozin in this study of elderly patients aged ≥65 years differed little from the incidence in the preapproval clinical trials. It was shown that tofogliflozin significantly decreased glycated hemoglobin levels.

Safety and efficacy of canagliflozin in elderly patients with type 2 diabetes mellitus: a 1-year post-marketing surveillance in Japan

“…The incidence of polyuria/pollakiuria was 1.31% in this survey, and the rate is almost the same with those (2.00% and 2.92%) reported in the analyses of PMS conducted in Japan for other SGLT2 inhibitors 7,8 . In this PMS of canagliflozin, skin-related ADRs occurred in 26 patients (1.89%), which were similar to the PMS of other SGLT2 inhibitors in Japanese elderly patients: 3.16% with ipragliflozin and 2.39% tofogliflozin, respectively 7,8 .…”

“…The incidence of polyuria/pollakiuria was 1.31% in this survey, and the rate is almost the same with those (2.00% and 2.92%) reported in the analyses of PMS conducted in Japan for other SGLT2 inhibitors 7,8 . In this PMS of canagliflozin, skin-related ADRs occurred in 26 patients (1.89%), which were similar to the PMS of other SGLT2 inhibitors in Japanese elderly patients: 3.16% with ipragliflozin and 2.39% tofogliflozin, respectively 7,8 . Over half of the ADRs related to skin complications are reported to occur within 30 days after the start of ipragliflozin treatment 7 , and the onsets are reported to be within the 4 weeks of tofogliflozin treatment among the one-third of the patients who experienced these disorders 8 .…”

“…Four-hundred and seventy-four patients (34.5%) withdrew from this survey. Although this withdrawal rate was high, it was similar to the PMS results of other SGLT2 inhibitors for elderly patients with T2DM; 39.4% of patients discontinued ipraglifloizin 7 , and 36.4% of patients discontinued tofogliflozin 8 , respectively. As for safety, a total of 9.09% (125/1375) of patients experienced ADRs during the survey period, which was lower than the 29.1% (474/ 1629) reported in previous Japanese clinical trials of canagliflozin 9 .…”

“…The demographic and baseline clinical characteristics of patients in this survey (e.g. sex ratio, average age, duration of diabetes, comorbidities of diabetic complications, hypertension, hyperlipidemia and concomitant use of other anti-diabetics) were similar to those reported in PMS previously conducted in Japan for other SGLT2 inhibitors 7,8 , showing no major differences in the actual prescription status between the SGLT2 inhibitors in Japan. Four-hundred and seventy-four patients (34.5%) withdrew from this survey.…”

“…As for safety, a total of 9.09% (125/1375) of patients experienced ADRs during the survey period, which was lower than the 29.1% (474/ 1629) reported in previous Japanese clinical trials of canagliflozin 9 . On the other hand, our survey had high withdrawal rate due to AEs (7.9%); however, such a high withdrawal rate is common to the PMS results of other SGLT2 inhibitors for elderly diabetic patients; ipragliflozin: 11.9% 7 and tofogliflozin: 12.6% 8 , respectively. Most of the patients who experienced ADRs (total number of 125 patients) also withdrew from this survey.…”