Safety and effectiveness of empagliflozin in Japanese patients with type 2 diabetes: interim analysis from a post-marketing surveillance study

Abstract

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are effective treatments for type 2 diabetes mellitus (T2DM). We present the interim findings of an ongoing post-marketing surveillance (PMS) study in Japanese patients with T2DM receiving empagliflozin. Research design and methods: This 3-year, prospective, observational, multicenter PMS evaluated the safety and effectiveness of empagliflozin in Japanese clinical practice. Patients with T2DM who had not been treated with empagliflozin before enrollment were eligible. Assessments, including the primary endpoint of incidence of adverse drug reactions (ADRs), were based on electronic case report forms (eCRF). Results: Of 8,180 registered patients from 1,103 sites, 7,618 patients had an eCRF including a follow-up visit and were treated (mean age, 58.8 years; 10.5% aged ≥75 years; 63.2% male; mean HbA1c, 8.01%; 41.8% with HbA1c ≥8.0%; 24.8% and 61.8% with at least mild hepatic and renal impairment, respectively). Mean treatment duration was 98.4 weeks; 644 (8.5%) patients had ≥1 ADR, including 8.5% of patients aged ≥75 years. Hypoglycemia, urinary tract infection, genital infections, volume depletion, diabetic ketoacidosis, and lower limb amputation occurred in 0.28%, 0.62%, 0.53%, 0.33%, 0%, and 0.03% of patients, respectively. Conclusions: The reported ADRs were consistent with the known safety profile of empagliflozin. Trial registration: ClinicalTrials.gov identifier: NCT02489942.

Real-World Evidence for Long-Term Safety and Effectiveness of Ipragliflozin in Japanese Patients with Type 2 Diabetes Mellitus: final Results of a 3-Year Post-Marketing Surveillance Study (STELLA-LONG TERM)

“…In this study, 38.8% of polyuria/pollakiuria events occurred within 7 days after administration, and most events (89.4%) recovered or were in remission. A relatively high incidence of polyuria/ pollakiuria has also been reported in the interim reports of post-marketing surveillance studies of the other SGLT2 inhibitors in Japanese T2DM patients [32,33,34,35]. This ADR may be expected based on the mechanism of action of SGLT2 inhibitors, which have been shown to increase urine volume [36], although the actual change in urine volume was not evaluated in this study.…”

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)

“…Collectively, these results should provide assurance to patients and physicians about the overall safety of tofogliflozin during long‐term use. Based on indirect comparisons, the incidence of overall ADRs (12.61%) observed in this surveillance is equivalent to that of the other post‐marketing studies of SGLT2 inhibitors (ipragliflozin, 10.71% over a period of 2 years 33 ; canagliflozin, 9.09% over a period of 1 year 34 ; empagliflozin, 8.5% over a period of 3 years 35 ).…”

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 – 21 ]. Most of the ADRs with an incidence of ≥ 0.1% have already been listed in the package insert for canagliflozin [ 1 ].…”