Long-Term Safety and Efficacy of Sitagliptin for Type 2 Diabetes Mellitus in Japan: Results of a Multicentre, Open-Label, Observational Post-Marketing Surveillance Study.

INTRODUCTION: A post-marketing surveillance (PMS) study was conducted to confirm the long-term risk-benefit profile of sitagliptin administered to Japanese patients with type 2 diabetes mellitus (T2DM) under real-world conditions. METHODS: This prospective, multicentre, open-label PMS collected data from 3326 patients receiving sitagliptin according to the approved indication during the case registration period (July 2010-June 2012; observation period, 3 years). Safety was assessed via collection of data on adverse drug reactions (ADRs), estimated glomerular filtration rate (eGFR) and cardiovascular events whereas efficacy was assessed via changes in glycated hemoglobin (HbA1c). RESULTS: In 3265 patients evaluated for safety, 270 ADRs occurred in 207 (6.3%) patients overall. Metabolism and nutrition disorders were the most common class of ADRs, occurring in 58 patients overall (53 non-serious, 5 serious) with hypoglycaemia (17 patients, 0.52%) the most common ADR. In patients with eGFR > 90 mL/min/1.73 m2 at baseline (mean ± SD, 106.42 ± 18.11 mL/min/1.73 m2, n = 584), eGFR declined by 11.83 ± 17.53 mL/min/1.73 m2 (P < 0.0001; n = 360) over the observation period whereas eGFR appeared to be relatively maintained in patients with lower baseline eGFR levels. Cardiovascular events were infrequent [occurring in 4 of 84 (4.76%) patients at high cardiovascular risk] with no distinct features in this Japanese population and the cumulative incidence [8.42% (3.12-21.70) at 36 months; n = 32] was similar to that noted in previous studies involving sitagliptin. In patients evaluated for efficacy, the overall change in HbA1c from baseline to final evaluation was mean ± SD - 0.68 ± 1.34% (P < 0.0001, n = 2070). Reductions in HbA1c tended to be greater in younger patients and patients with higher body mass index (BMI) and HbA1c values at the start of administration. CONCLUSION: Long-term sitagliptin administration in the routine clinical practice setting is associated with good efficacy, including as monotherapy, with no additional safety concerns.

Real-world evidence of the safety and efficacy profile of suvorexant in elderly patients with insomnia: a sub-analysis of the post-marketing drug-use results survey in Japan.

Objective: Global Phase III trials of suvorexant showed no obvious differences in the safety and efficacy profile of suvorexant between elderly and non-elderly patients. However, the clinical profile of suvorexant in elderly patients with comorbidities in a real-world setting was not evaluated. To further understand the safety and efficacy profile of suvorexant in elderly patients with insomnia in a daily clinical practice setting, we conducted a sub-group analysis of the post-marketing drug-use results survey.Methods: Patients with insomnia who were treated with suvorexant for the first time were divided into three groups: group-1 (<65 years, N = 1490), group-2 (≥65 years and <75 years, N = 730), and group-3 (≥75 years, N = 1028).Results: The incidence of overall adverse drug reactions (ADRs) were 11.28% (N = 168), 8.63% (N = 63), and 8.17% (N = 84) in group-1, -2, and -3, respectively. The ADRs most commonly observed in this survey were somnolence, insomnia, and dizziness, with no new safety concerns or differences in safety issues found. The numbers of patients in group-1, -2, and -3 who visited internal medicine departments were: 690 patients (46.3%), 521 patients (71.4%), and 793 patients (77.1%), respectively. The percentage of patients who were deemed to have "improved", based on the patient's self-assessment and their physician's assessment, was 70-75% of patients in all groups.Conclusion: These results reveal the safety and efficacy profile of suvorexant in elderly patients who often have various and multiple comorbidities and were treated in a daily clinical practice setting.

Safety profile and clinical course of patients with insomnia administered suvorexant by initial treatment status in a post-marketing survey.

Objectives: Suvorexant is a dual orexin receptor antagonist used for treating insomnia. The authors elucidated the safety profiles and clinical course of insomnia therapy with suvorexant under different initial treatment status seen in daily routine practice. Methods: Subgroup analysis of a post-marketing survey (PMS; 2015-2017) divided patients based on their initial treatment status with suvorexant into 'hypnotic-naïve (Group N)', 'switching from a prior sleep medication (Group S),' 'add-on therapy (Group A),' and 'others (Group O).' Results: Among 3248 patients analyzed in the PMS, the number of patients in Groups N, S, A, and O was 1946 (59.9%), 703 (21.6%), 536 (16.5%), and 63 (1.9%), respectively. The incidence of insomnia-related adverse drug reactions (ADRs) in Group S (5.3%) tended to be higher than that in Groups N (0.46%) and A (1.5%). Discontinuation rate due to an inadequate effect at 6 months in Group S (14.9%) tended to be higher than that in Groups N (9.6%) and A (10.4%). Conclusion: The results suggest that initiating suvorexant treatment after switching from other insomnia medication must require careful monitoring of insomnia-related ADRs, which might be due to abrupt discontinuation of the prior insomnia medication use.

Suvorexant (Belsomra® Tablets 10, 15, and 20 mg): Japanese Drug-Use Results Survey.

BACKGROUND: We report on the results of a Japanese postmarketing drug-use survey of suvorexant (Belsomra®) tablets. METHODS: A survey with a ≤ 6-month observation period after the start of administration was conducted, targeting insomnia patients who were treated with suvorexant for the first time in Japan. Information on the safety and efficacy of the drug product was collected. The evaluation period was July 21, 2015-August 12, 2017, and the target number of patients was 3428. RESULTS: The mean administration period for the safety analysis population of 3248 patients was 113 days. At 6 months after the start of treatment, 48.6% (1577/3248) of the patients had been continually receiving treatment, and 51.4% (1671/3248) of the patients discontinued/dropped out of treatment before 6 months. Among the patients who discontinued/dropped out of the treatment, more than 30% discontinued due to improvement. The mean treatment duration for those who had discontinued treatment for this reason was 62 days. The incidence rate of adverse drug reactions among those in the safety analysis population was 9.7%, and the common adverse drug reactions were somnolence (3.6%), insomnia (1.2%), dizziness (1.1%), and nightmare (0.8%), all of which are described in the product label. No additional noteworthy events were observed. In 2439 patients with a final overall global assessment of sleep judged by physicians, the 'improved' rate was 74.0%. Among 2424 patients who provided a final overall global assessment, the improvement rate was 73.2%, which was comparable with the improvement rate judged by physicians. Regarding clinical effects (based on patient diary data or physician's assessment), reduction in median sleep latency and increase in median total sleep time (reduction from 60 to 50 min and increase from 300 to 360 min compared with baseline, respectively) were observed at 1 week after the start of treatment and onwards, and the effect was maintained after the start of treatment for 6 months. A similar effect was observed irrespective of age groups or reasons for using suvorexant. CONCLUSION: This survey was an exploratory observational study without a control group; the interpretation of results may require the consideration of factors that may have caused bias in the results, such as demographic characteristics and effects of other drugs. However, the results suggest that suvorexant can be a useful drug in daily clinical practice for treating insomnia.

Safety and effectiveness, including intelligence prognosis, of diazoxide in pediatric patients with hyperinsulinemic hypoglycemia: special survey in Japan (long-term, all-case survey).

To evaluate the safety and effectiveness of the long-term administration of diazoxide in patients with hyperinsulinemic hypoglycemia, a post-marketing surveillance study was conducted. Between 2008 and 2015, with a maximum observation period of 7 yr, 384 patients were monitored; 117 (30.5%) experienced at least one adverse drug reaction (ADR). The most commonly observed ADR was hypertrichosis (8.6%). The incidence of water retention-related ADRs and cardiac failure-related ADRs was 8.3% and 3.4%, respectively, and many of these occurred within the first 2 mo of treatment. The mean fasting blood glucose level was 44.9 mg/dL at baseline and was maintained at > 70 mg/dL, the control target, for 4 yr. A total of 113 infants < 1 yr of age were evaluated for the prognosis for intelligence, and a majority (77.9%) were assessed as "normal" at the final evaluation. Most ADRs occurred at an early stage of treatment and blood glucose levels were well controlled during long-term administration. The proportion of "normal" patients tended to be higher in those who started treatment at a younger age. However, because of the exploratory nature of this analysis, potential effects of coexisting or underlying diseases and the age of onset or diagnosis should not be ignored.