A Disproportionality Analysis of the Adverse Effect Profiles of Methimazole and Propylthiouracil in Patients with Hyperthyroidism Using the Japanese Adverse Drug Event Report Database.

Background: Antithyroid drugs (ATDs) are frequently used to achieve euthyroidism in patients with hyperthyroidism. ATDs cause characteristic common and rare adverse events; however, comprehensive comparisons between methimazole (MMI) and propylthiouracil (PTU) in terms of adverse events are limited. Methods: In this study, we thoroughly explored adverse events in association with MMI and PTU use with a disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database and evaluated the prevalence of MMI and PTU prescriptions using the National Database of Health Insurance Claims and Specific Health Checkups (NDB) Open Data Japan. We analyzed 3271 cases of MMI use and 1029 cases of PTU use with respect to 9789 preferred terms (PTs) for adverse events registered in the JADER database by calculating and comparing reporting odds ratios (RORs). Results: We found that 8 PTs, including agranulocytosis (p < 0.0001, 4.01-fold), aplasia cutis congenita (p < 0.0001, 123.22-fold), and exomphalos (p = 0.0002, 22.17-fold), demonstrated significantly higher RORs (more than 4-fold) for MMI use than for PTU use. Nineteen PTs, including anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (p < 0.0001, 29.84), rapidly progressive glomerulonephritis (p < 0.0001, 6.44), and pulmonary alveolar hemorrhage (p < 0.0001, 7.77), had RORs for PTU use more than four times those for MMI use. NDB Open Data Japan showed more frequent PTU prescriptions than MMI prescriptions for women of reproductive age. Conclusions: This large-scale study confirmed that a variety of congenital malformations were identified as having significantly high RORs for MMI use, while diseases related to ANCA-associated vasculitis were specific to PTU.

Abdominal aortic calcification is associated with Fibrosis-4 index and low body mass index in type 2 diabetes patients: A retrospective cross-sectional study.

AIMS/INTRODUCTION: This study aimed to clarify the nature of the relationship between the abdominal aortic calcification (AAC) grade and the presence of cardiovascular diseases, and determine factors related to AAC grade in people with type 2 diabetes mellitus. MATERIALS AND METHODS: This retrospective cross-sectional study enrolled 264 inpatients with type 2 diabetes mellitus. The AAC score and length were measured using the lateral abdominal radiographs. Logistic regression models were used to assess the associations between AAC scores/lengths and the presence of coronary artery disease (CAD), cerebral infarction (CI) and peripheral artery disease (PAD). The correlation between AAC scores/lengths and other clinical factors were evaluated using linear regression models. RESULTS: The AAC score was significantly correlated with prevalent CAD and CI independent of age and smoking, but not with the prevalence of PAD. AAC length was not significantly correlated with the presence of CAD, CI or PAD; however, the sample size was insufficient to conclude, probably due to low prevalence. Both the AAC score and length were correlated inversely with body mass index (BMI) and, with the Fibrosis-4 (Fib-4) index >2.67; these correlations were significant after adjusting for cardiovascular risk factors and BMI, although AAC was not associated with ultrasonography-diagnosed fatty liver. There was a significant interaction between BMI and Fib-4 index; lower BMI and Fib-4 index >2.67 showed a synergistic association with high AAC grade. CONCLUSIONS: AAC score is associated with CAD and CI morbidity in participants with type 2 diabetes mellitus. Low BMI and Fib-4 index >2.67 can be valuable indicators of AAC in people with type 2 diabetes mellitus.

Immediate Glucose-Lowering Effect After the First Administration of Dulaglutide: A Retrospective, Single-Center, Observational Study.

INTRODUCTION: Dulaglutide is a long-acting glucagon-like peptide 1 receptor agonist that is administered once weekly for the treatment of type 2 diabetes. However, the immediate glucose-lowering effect of dulaglutide after the first administration and the factors affecting the efficacy of the drug remain unclear. METHODS: This study was a retrospective and observational study of 80 subjects with type 2 diabetes conducted in a hospitalized setting. The changes (Δ) in the blood glucose (BG) levels at six time points (6-point BG levels) from the baseline (day - 1) to the day after the first administration of 0.75 mg of dulaglutide (day 1) were evaluated. The associations of the Δ 6-point BG levels with the patients' characteristics and laboratory data were also analyzed. RESULTS: Significant reduction of the fasting BG, preprandial BG, postprandial BG, and standard deviation (SD) of the 6-point BG levels was observed on day 1 as compared to day - 1 (P < 0.0001) and the reduced BG levels were maintained throughout the remaining observation period of 5 days. The baseline serum hemoglobin A1c and glycoalbumin levels were positively correlated with the reduction of the fasting BG. The Δ BG levels were not related to the parameters of insulin-secreting capacity. Insulin treatment was positively associated with the reduction of the 6-point BG levels. Patients without cerebrovascular disease and patients without diabetic retinopathy showed greater improvements of the fasting BG and SD of the 6-point BG levels, respectively. Urinary microalbumin level was positively correlated with improvements of the 6-point BG levels. Dulaglutide reduced the BG levels, irrespective of the previously used class of antidiabetic medication(s). CONCLUSION: Dulaglutide achieved reduction in glucose level within 24 h of the first injection. The improvement in the BG levels remained stable for a week in the hospitalized clinical setting.

Drug-induced hyperglycemia in the Japanese Adverse Drug Event Report database: association of evelolimus use with diabetes.

Some categories of drugs are known for causing hyperglycemia or diabetes such as steroids, antipsychotics, and immunosuppressant. However, there has been little evidence from studies about the proportion of each drug in the context of drug-induced diabetes. In this study, we used data from the Japanese Adverse Drug Event Report (JADER) database, a spontaneous reporting system database maintained at the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan, reported between April 2004 and June 2017. Among 459,250 reports of adverse drug reactions in JADER database, reported instances of the adverse event of hyperglycemia or diabetes were extracted. After the exclusion of anti-diabetes drugs, the drugs frequently implicated in the development of hyperglycemia or diabetes, including prednisolone, tacrolimus, everolimus, ribavirin, quetiapine, aripiprazole, interferon alfa-2b, risperidone, atorvastatin, dexamethasone, ciclosporin, nilotinib, methylprednisolone, or nivolumab, were identified. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, was manifested as the third most frequently associated drug with hyperglycemia or diabetes (340 cases), following prednisolone (694 cases) and tacrolimus (393 cases), and the reporting odds ratio (ROR 8.56, 95% CI 7.65-9.57) of this drug was higher than that of the two aforementioned drugs (ROR 3.96, 95% CI 3.66-4.28 and ROR 3.51, 95% CI 3.17-3.89). These results suggest that there is a potent association of evelolimus with hyperglycemia in clinical practice in Japan.