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.

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.

Aims/Introduction: Tofogliflozin is a potent and highly selective sodium-glucose cotransporter 2 inhibitor, and is currently used to treat patients with type 2 diabetes mellitus. We designed a 3-year study of tofogliflozin in patients with type 2 diabetes mellitus to evaluate the safety and effectiveness in routine clinical practice. The 3-and 12-month interim analysis showed tofogliflozin was well-tolerated, safe and clinically effective. Here, we report the results of the 24-month interim analysis. Materials and Methods: This is a 3-year prospective, observational and multicenter post-marketing study (Japanese Study of Tofogliflozin with Type 2 Diabetes Mellitus Patients/Long Term). Results: Of the 6,897 patients enrolled, 6,712 and 6,461 patients were analyzed for the safety and effectiveness of tofogliflozin, respectively. During the 24-month observation period, the incidence rates of adverse drug reactions (ADRs) and serious adverse drug reactions were 11.25 and 1.21%, respectively. As to adverse drug reactions of special interest, the incidence rates of hypoglycemia, polyuria/pollakiuria, volume depletion-related events, urinary tract infections and genital infection were 0.83, 1.28, 1.46, 1.18 and 1.62%, respectively. Renal disorders, and cardiovascular and cerebrovascular disorders occurred in 0.63 and 0.76% of the patients, respectively. Glycated hemoglobin A1c and bodyweight decreased significantly by −0.70% (P < 0.0001) and −2.95 kg (P < 0.0001), respectively, from baseline to week 104 (last observation carried forward). Conclusions: Significant safety concerns have not been observed, and clinical benefit including a long-term reduction in glycated hemoglobin A1c over a 104-week (24 months) observation period with weight loss was suggested in this 24-month interim analysis of the 3-year Japanese Study of Tofogliflozin with Type 2 Diabetes Mellitus Patients/Long Term in routine clinical practice.

Aims/IntroductionDue to the paucity of tofogliflozin data, we assessed the safety and effectiveness of tofogliflozin among Japanese patients with type 2 diabetes mellitus in the clinical setting, stratifying the patients by age, sex, estimated glomerular filtration (eGFR) rate and body mass index. We report the results of a 12‐month interim analysis.Materials and MethodsThis was a 3‐year prospective, observational and multicenter post‐marketing study (Japanese Study of tofogliflozin with type 2 diabetes mellitus Patients/Long Term).ResultsOut of 6,897 patients enrolled, the safety and effectiveness analysis populations consisted of 6,712 and 6,449 patients, respectively. During 12 months, adverse drug reactions and their incidence were 9.12 and 0.88%, respectively. The incidence of hypoglycemia was 0.67%. Polyuria/pollakiuria occurred more frequently in patients aged ≥65 years than in patients aged <65 years. Women experienced higher rates of urinary tract and genital infection than men. The lowest eGFR subgroup experienced maximum volume depletion‐related events. Cardiovascular and cerebrovascular disorders occurred in 0.55% of the patients. Glycated hemoglobin (HbA1c) and bodyweight significantly decreased by −0.76% and −2.73 kg, respectively, from baseline to the last observation carried forward (P < 0.0001). Except for the lowest eGFR subgroup, other eGFR subgroups showed significantly decreased HbA1c values. All eGFR subgroups showed significantly decreased bodyweight, and all body mass index subgroups showed significantly decreased HbA1c and bodyweight.ConclusionsOur interim 12‐month data suggest that tofogliflozin could be used safely and effectively in Japanese patients with type 2 diabetes mellitus, as tofogliflozin was well tolerated with low hypoglycemia risk, and significantly improved HbA1c and bodyweight.

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.

Aims/Introduction This subanalysis aimed to assess the safety and effectiveness of tofogliflozin by using data from the Japanese Study of Tofogliflozin with Type 2 Diabetes Mellitus Patients in an Observational Study of the Elderly to categorize elderly Japanese patients with type 2 diabetes mellitus by the number of concomitant oral antidiabetic drugs (OADs) and insulin use at baseline. Materials and Methods Japanese Study of Tofogliflozin with Type 2 Diabetes Mellitus Patients in an Observational Study of the Elderly is a 1‐year prospective, observational and multicenter post‐marketing study that enrolled all patients with type 2 diabetes mellitus aged ≥65 years who started tofogliflozin during the first 3 months after its launch in May 2014 in Japan. Results The safety and effectiveness analysis sets included 1,497 and 1,422 patients, respectively. Overall, 18.10 and 2.20% of the patients experienced adverse drug reactions (ADRs) and serious ADRs, respectively. ADRs of special interest in the total, 0 OAD, one OAD, two OADs, three or more OADs and insulin groups occurred in 12.22, 10.04, 12.35, 13.32, 11.27 and 14.91% of patients, respectively. Volume depletion‐related events were the most frequently observed ADRs of special interest. Hypoglycemia occurred in 1.07% of patients. Overall, glycated hemoglobin and bodyweight were significantly decreased, but the estimated glomerular filtration rate was not significantly changed. Conclusions Our finding suggests that tofogliflozin could be safely and effectively used in elderly Japanese patients with type 2 diabetes mellitus, irrespective of the number of OADs and the use of insulin.

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