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).

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.

Correction to: Safety and efficacy of ripasudil in Japanese patients with glaucoma or ocular hypertension: 12-month interim analysis of ROCK-J, a post-marketing surveillance study.

An amendment to this paper has been published and can be accessed via the original article.

Safety and efficacy of ripasudil in Japanese patients with glaucoma or ocular hypertension: 12-month interim analysis of ROCK-J, a post-marketing surveillance study.

BACKGROUND: Ripasudil is approved in Japan for glaucoma or ocular hypertension (OH) when other treatments are ineffective or cannot be administered. Its long-term safety and efficacy are being examined in a post-marketing surveillance study; 12-month data are described here. METHODS: This prospective, open-label, observational study enrolled patients with glaucoma or OH who started ripasudil during routine care. The key safety outcome was the incidence of adverse drug reactions (ADRs), focusing on allergy and/or inflammation-related ADRs such as blepharitis (including allergic) or conjunctivitis (including allergic). The primary efficacy endpoint was least squares mean (LSM) ± standard error (SE) change in intraocular pressure (IOP) from baseline to 12 months in all patients and in diagnostic groups. Secondary endpoints were change in IOP in groups stratified by treatment initiation pattern, number of concomitant drugs, and baseline IOP. RESULTS: Overall, 3359 patients (48% male, mean age ± standard deviation [SD] 69.1 ± 12.7 years) were evaluated for safety and 3323 for efficacy. Diagnoses were primary open-angle glaucoma (43.9%), normal-tension glaucoma (36.6%), secondary glaucoma (8.7%), OH (4.2%), and primary closed-angle glaucoma (2.4%). Mean ± SD observation period was 300.1 ± 122.4 days; 1010 patients (30.1%) discontinued ripasudil by 12 months. ADRs occurred in 626 patients (18.6%); the most common were conjunctival hyperemia and blepharitis. Allergy and/or inflammation-related ADRs occurred in 388 patients (11.6%), most commonly blepharitis (5.6%) and conjunctivitis (4.2%). IOP decreased significantly from a mean ± SD 18.1 ± 6.1 mmHg at baseline; the LSM ± SE IOP change throughout 12 months of ripasudil treatment was - 2.6 ± 0.1 mmHg (- 14.0 ± 0.4%; p < 0.001). A significant decrease in IOP at 12 months was seen in all categories of baseline IOP (p < 0.001), and all types of glaucoma (p < 0.001), except neovascular glaucoma. Ripasudil was associated with a significant reduction in IOP at 12 months whether initiated as monotherapy or in combination with ≤4 concomitant glaucoma therapies (p < 0.001). CONCLUSIONS: Ripasudil was safe and effective in patients with glaucoma or OH during routine care. No new safety signals were identified, and significant reductions in IOP were maintained over 12 months.

Safety and effectiveness of tofogliflozin in Japanese patients with type 2 diabetes mellitus: Results of 24-month interim analysis of a long-term post-marketing study (J-STEP/LT).

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.

Safety and effectiveness of tofogliflozin in Japanese patients with type 2 diabetes mellitus in real-world practice: Results of 12-month interim analysis of a long-term post-marketing surveillance study (J-STEP/LT).

AIMS/INTRODUCTION: Due 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 METHODS: This was a 3-year prospective, observational and multicenter post-marketing study (Japanese Study of tofogliflozin with type 2 diabetes mellitus Patients/Long Term). RESULTS: Out 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. CONCLUSIONS: Our 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.

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

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.

Long-term safety and efficacy of the sodium-glucose cotransporter 2 inhibitor, tofogliflozin, added on glucagon-like peptide-1 receptor agonist in Japanese patients with type 2 diabetes mellitus: A 52-week open-label, multicenter, post-marketing clinical study.

AIMS/INTRODUCTION: Tofogliflozin is a potent and highly selective sodium-glucose cotransporter 2 inhibitor that is currently used to treat patients with type 2 diabetes mellitus. The aim of the present study was to evaluate the safety and efficacy of tofogliflozin add-on to glucagon-like peptide-1 (GLP-1) receptor agonist monotherapy. MATERIALS AND METHODS: In this 52-week, prospective, multicenter, single arm, post-marketing clinical study, Japanese patients who had already been receiving GLP-1 receptor agonist monotherapy for ≥8 weeks, glycated hemoglobin ≥7.0 and <10.5%, and body mass index ≥18.5 and <35.0 kg/m2 were enrolled. Tofogliflozin 20 mg was orally administered once daily for 52 weeks with GLP-1 receptor agonist. Primary end-points were safety and change in glycated hemoglobin from baseline to week 52. Safety was assessed on the basis of the adverse events. Changes from baseline in fasting plasma glucose, bodyweight, blood pressure, uric acid and lipid parameters were assessed as secondary efficacy end-points. RESULTS: Of the 67 patients enrolled, 63 patients completed the study. Overall, 26 adverse drug reactions occurred in 17 patients (25.4%). Adverse drug reactions with a frequency of two or more patients (3.0%) were constipation, thirst, dehydration and pollakiuria. Hypoglycemia (n = 1) was limited. With the addition of tofogliflozin to GLP-1 receptor agonist, the subsequent mean (standard deviation) reduction in glycated hemoglobin was -0.6% (1.0%; P < 0.0001). Fasting plasma glucose, bodyweight and blood pressure were significantly improved. CONCLUSIONS: Tofogliflozin add-on to GLP-1 receptor agonist monotherapy is an effective treatment option with an acceptable safety profile.

Correction to: Safety and Efficacy of Ripasudil in Japanese Patients with Glaucoma or Ocular Hypertension: 3-month Interim Analysis of ROCK-J, a Post-Marketing Surveillance Study.

In the original publication values in the results section are incorrect. Errors were also identified in Fig. 5.

Safety and efficacy of tofogliflozin in Japanese patients with type 2 diabetes mellitus in real-world clinical practice: Results of 3-month interim analysis of a long-term post-marketing surveillance study (J-STEP/LT).

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.

Safety and Efficacy of Ripasudil in Japanese Patients with Glaucoma or Ocular Hypertension: 3-month Interim Analysis of ROCK-J, a Post-Marketing Surveillance Study.

INTRODUCTION: To evaluate the safety and intraocular pressure (IOP)-lowering effects of a ripasudil 0.4% ophthalmic solution in Japanese patients with glaucoma and ocular hypertension (OH) as a post-marketing surveillance. METHODS: This was a 2-year prospective observational study in patients with glaucoma or OH who had not previously received ripasudil. Patients registered in the study using a central internet-based system from June 1, 2015 to April 30, 2017. Data on adverse drug reactions (ADRs) and IOP were collected and analysed from the first 3 months of ripasudil treatment. RESULTS: Of the 3058 patients in the safety analysis set, 3016 had IOP data and were included in the efficacy analysis. ADRs were seen in 244 (8.0%) of the 3058 patients. IOP decreased significantly in patients with primary open-angle glaucoma (- 2.9 ± 4.2 mmHg; p < 0.001), normal tension glaucoma (- 1.7 ± 2.4 mmHg; p < 0.001), primary angle-closure glaucoma (- 3.9 ± 5.3 mmHg; p < 0.001), and OH (- 3.8 ± 5.8 mmHg; p < 0.001). Significant IOP reduction was also noted in exfoliation glaucoma (- 3.0 ± 5.5 mmHg; p < 0.001), uveitis-associated glaucoma (- 4.7 ± 7.2 mmHg; p < 0.001) and steroid glaucoma (- 5.5 ± 6.0 mmHg; p < 0.001), but not for neovascular glaucoma (- 2.8 ± 12.1 mmHg; p = 0.669). CONCLUSION: Ripasudil was safe and effective in the treatment of glaucoma and OH in Japanese patients, with a low incidence of ADRs or treatment discontinuation, and reduced IOP after 3 months of treatment. FUNDING: Kowa Company, Ltd., Tokyo, Japan.

Long-term safety and efficacy of tofogliflozin as add-on to insulin in patients with type 2 diabetes: Results from a 52-week, multicentre, randomized, double-blind, open-label extension, Phase 4 study in Japan (J-STEP/INS).

AIMS: To evaluate the long-term safety and efficacy of tofogliflozin as an add-on treatment to insulin over 52 weeks. MATERIALS AND METHODS: This 52-week, multicentre, Phase 4 study consisted of a 16-week, randomized, double-blind, placebo-controlled phase and a 36-week open label extension phase (NCT02201004). Japanese patients with type 2 diabetes mellitus, aged 20 to 75 years, with suboptimal glycaemic control (7.5%-10.5%) receiving insulin monotherapy (basal-bolus, bolus, premix [low and high] and basal) or receiving combination therapy with basal insulin and dipeptidyl peptidase-4 inhibitor were eligible for participation. Patients who received tofogliflozin throughout the study (52 weeks) were referred to as the 'tofo-tofo group' and patients who received placebo and tofogliflozin (36 weeks) were referred to as the 'pla-tofo group'. RESULTS: A total of 210 patients received treatment per randomization. Hypoglycaemia was the most common treatment-emergent adverse event (AE) (42.9% in the tofo-tofo group and 29.4% in the pla-tofo group). Patients reported genital infection, urinary tract infection, excessive urination and AEs related to volume depletion (2.1%, 2.1%, 7.1% and 10.0% of patients in the tofo-tofo group, and 0%, 1.5%, 2.9% and 7.4% of patients in the pla-tofo group, respectively). Mean HbA1c and body weight at baseline (mean changes ± standard error from baseline to Week 52) in the tofo-tofo and pla-tofo groups were 8.53% (-0.76% ± 0.077) and 8.40% (-0.73% ± 0.102); 68.84 kg (-1.52 kg ± 0.207) and 72.24 kg (-2.13 kg ± 0.313), respectively. CONCLUSIONS: This study demonstrates the safety and efficacy of tofogliflozin as add-on to insulin therapy in type 2 diabetes mellitus patients, offering a new therapeutic solution to diabetes management.

Efficacy and safety of tofogliflozin in Japanese patients with type 2 diabetes mellitus with inadequate glycaemic control on insulin therapy (J-STEP/INS): Results of a 16-week randomized, double-blind, placebo-controlled multicentre trial.

AIMS: To assess the effects of 16 weeks of tofogliflozin (sodium-glucose co-transporter-2 [SGLT2] inhibitor) treatment vs placebo on glycated haemoglobin (HbA1c) levels in Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with insulin monotherapy or insulin plus a dipeptidyl peptidase-4 (DPP-4) inhibitor. METHODS: The study comprised a 16-week, multicentre, double-blind, placebo-controlled period and a 36-week extension (NCT02201004). Men and women (aged ≥20 and ≤75 years) with T2DM (HbA1c ≥7.5% and ≤10.5%) were randomized 2:1 to tofogliflozin 20 mg once/day or placebo. The primary endpoint was change in HbA1c from baseline. Insulin reduction was not permitted during this study. RESULTS: A total of 211 patients were randomized (141 tofogliflozin, 70 placebo). Addition of tofogliflozin to insulin therapy was significantly superior to placebo for lowering HbA1c (-0.59 vs +0.48%; P < .0001), fasting plasma glucose (-27.2 vs +5.3 mg/dL; P < .0001), postprandial plasma glucose (-65.0 vs +3.2 mg/dL; P < 0.0001), serum uric acid (-0.18 vs +0.07 mg/dL; P = .0062), body weight (-1.34 vs +0.03 kg; P < .0001) and daily insulin dose (-1.3 vs -0.2 U, P = .0152). Hypoglycaemia occurred in 30.7% of patients receiving tofogliflozin vs 21.4% for placebo. Two patients treated with tofogliflozin each had a genital or urinary tract infection. CONCLUSIONS: This 16-week double-blind study indicated that, in patients with T2DM whose HbA1c levels were poorly controlled with insulin monotherapy or insulin plus a DPP-4 inhibitor, addition of tofogliflozin was an effective treatment option with an acceptable safety profile.

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

AIMS/INTRODUCTION: Although 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 METHODS: This 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. RESULTS: Of 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. CONCLUSIONS: The 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.

Effectiveness and safety of an extended-release tablet of sodium valproate for the prophylactic treatment of migraine: Postmarketing surveillance in Japan.

BACKGROUND: Sodium valproate is a standard drug for first-line prophylactic treatment of migraine. However, little information is available of its use in Japanese patients. AIM: To evaluate the effectiveness and safety of an extended-release tablet of sodium valproate in the prophylactic treatment for Japanese patients with migraine by postmarketing surveillance. METHODS: This was a prospective, multicenter and non-interventional observation study in routine clinical practice. A total of 1222 patients with migraine of all age groups (aged <10 to ≤80 years) and both sexes (17.3% men and 82.7% women) from 169 sites were enrolled. RESULTS: Migraine frequency during a 4-week period was reduced from 10.2 ± 6.0 days in 1040 patients to 5.0 ± 4.6 days in 944 patients (P < 0.001): 70.8% of patients experienced remission of migraine by ≥30%, 59.0% by ≥50% and 11.8% by ≥100%. Multivariate analysis and stratification sampling showed that this sodium valproate tablet was the most effective in patients with more migraine days, and complete remission was observed in 29% of patients whose migraine days were less than 3 days per 4 weeks at baseline. The extended-release tablet of sodium valproate reduced migraine intensity and duration of migraine attacks. The incidence of adverse drug reactions was 6.3% (67/1070 patients) and well tolerated. However, four pregnancies were discovered in this survey. CONCLUSIONS: This first large observation study in Japan suggests that an extended-release tablet of sodium valproate is effective and safe for the prophylactic treatment of patients with migraine in routine clinical practice.

Japanese study of tofogliflozin with type 2 diabetes mellitus patients in an observational study of the elderly (J-STEP/EL): A 12-week interim analysis.

AIMS/INTRODUCTION: Sodium-glucose co-transporter 2 inhibitors are a promising treatment for type 2 diabetes mellitus, but are associated with concerns about specific adverse drug reactions. We carried out a 1-year post-marketing surveillance of tofogliflozin, a novel agent in this class, in Japanese elderly patients with type 2 diabetes mellitus and here report the results of a 12-week interim analysis, focusing on adverse drug reactions of special interest. MATERIALS AND METHODS: The present prospective observational study included all type 2 diabetes mellitus patients aged ≥65 years who started tofogliflozin during the first 3 months after its launch. Data on demographic and baseline characteristics, clinical course and adverse events were collected. RESULTS: Of 1,535 patients registered, 1,506 patients whose electronic case report forms were collected and who had at least one follow-up visit were included in the safety analysis at 12 weeks. A total of 178 of 1,506 patients (11.82%) had at least one adverse drug reaction to tofogliflozin. The incidence of adverse drug reactions of special interest (polyuria/pollakiuria, volume depletion-related events, urinary tract infection, genital infection, skin disorders and hypoglycemia) was 2.19, 2.32, 1.33, 1.13, 1.46 and 0.73%, respectively. No new safety concerns were identified. Among those evaluable for clinical effectiveness, the mean (standard deviation) glycated hemoglobin decreased from 7.65% (1.35%) at baseline to 7.25% (1.16%) at 12 weeks by 0.39% (0.94%; P < 0.0001). CONCLUSIONS: This interim analysis characterized the safety profile of tofogliflozin in Japanese elderly patients with type 2 diabetes mellitus during the early post-marketing period.