Long-term safety and effectiveness of linagliptin as add-on therapy in Japanese patients with type 2 diabetes: final results of a 3-year post-marketing surveillance.

BACKGROUND: We investigated the long-term safety and effectiveness of linagliptin in Japanese type 2 diabetes (T2D) patients starting linagliptin add-on therapy in routine clinical practice. RESEARCH DESIGN AND METHODS: This 3-year prospective, observational, post-marketing surveillance (PMS) was conducted in Japanese patients starting linagliptin add-on therapy. The primary outcome was the incidence of adverse drug reactions (ADRs). The secondary outcome was the change from baseline in HbA1c. RESULTS: The safety analysis set comprised of 3,372 patients. Mean ± standard deviation (SD) age was 66.5 ± 12.4 years. Most patients (63.2%) received linagliptin in combination with another antidiabetic drug, most commonly a sulfonylurea (38.6%). The incidence of ADRs was 11.39%; the most common ADRs according to MedDRA preferred terms were diabetes mellitus (1.25%), hypertension (0.83%), and hypoglycemia (0.80%). In the effectiveness analysis set (n = 3,029), mean ± SD HbA1c was 7.76 ± 1.37% at baseline and 7.26 ± 1.19% at last observation; mean change from baseline to last observation was - 0.49 ± 1.33%; sustained reductions in HbA1c were observed. These results were consistent across patient subgroups. CONCLUSIONS: In this PMS, linagliptin add-on therapy for Japanese T2D patients had a safety profile consistent with its known profile and HbA1c reductions over 3 years were observed. CLINICALTRIALS.GOV: NCT01904383.

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.