Real-world evidence for the safety of ipragliflozin in elderly Japanese patients with type 2 diabetes mellitus (STELLA-ELDER): final results of a post-marketing surveillance study

Abstract

Objective: To investigate the real-world safety of ipragliflozin in elderly Japanese patients with type 2 diabetes mellitus (T2DM). Research design and methods: Japanese patients (≥65 years old) who were first prescribed ipragliflozin within 3 months after its launch in April 2014 were registered in this post-marketing surveillance (PMS). Final data collection was in July 2015. Survey items included demographics, treatments, adverse drug reactions (ADRs), vital signs, and laboratory variables. Results: The PMS included 8505 patients (4181 males/4324 females). The mean age and diabetes duration were 72.3 years and 10.6 years, respectively. In 84.3% of patients, ipragliflozin was prescribed at 50 mg/day, which was continued unchanged. Overall, 16.91% of patients experienced 1880 ADRs, and 165 ADRs were classified as serious in 127 patients (1.49%). ADRs of special interest included skin complications, volume depletion, polyuria/pollakiuria, genital infection, urinary tract infection, renal disorders, hypoglycemia, cerebrovascular disease, cardiovascular disease, malignant tumor, fracture, and ketone body-related events. Conclusions: This 1-year PMS revealed probable ADRs in elderly Japanese patients with T2DM prescribed ipragliflozin in real-world settings, with no new safety concerns. The risk factors for ADRs varied but could be rationalized. The results should help physicians to identify possible treatment-emergent ADRs in ipragliflozin-treated patients.ARTICLE HISTORY

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 .…”

“…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.…”

“…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 .…”

“…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 . On the other hand, these ADRs seemed not to occur in a specified period after the start of administration of canagliflozin in this PMS.…”