Osteoporosis or fracture risk associated with thiazolidinedione and proton pump inhibitor co-administration in patients with type 2 diabetes mellitus.

WHAT IS KNOWN AND OBJECTIVE: Thiazolidinedione (TZD) and proton pump inhibitor (PPI) belong to classes of drugs that affect bone metabolism; however, few studies have investigated the effects of these drugs on bone metabolism. The aim of this study was to assess the risk of osteoporosis or fracture in patients with type 2 diabetes mellitus (T2DM) co-administered TZD and PPIs. METHODS: This retrospective cohort study was conducted using the National Sample Cohort database from 2003 to 2013. We included adult patients with T2DM who were prescribed TZD and PPIs together for the first time. The Cox proportional hazard model was used to determine the risk ratio of fracture or osteoporosis in the co-administration cohort (TZD + PPI) compared with the TZD-only group (TZD). We adjusted for age, sex, use of other medications and other diseases that affect the bone. RESULTS AND DISCUSSION: Of 9073 patients administered TZD, the number of eligible patients was 7240 (545 TZD + PPI, 6695 TZD-only). After 1:3 propensity score matching, 545 patients remained in the TZD + PPI group and 1635 in the TZD-only group. The risk of osteoporosis or fracture was significantly higher in the TZD + PPI cohort than in the TZD-only cohort. The adjusted hazard ratio (HR) for fracture or osteoporosis was 1.47 (95% CI 1.05-2.07). TZD and PPI use in women were associated with an increased risk of skeletal outcomes. WHAT IS NEW AND CONCLUSION: TZD and PPI use were associated with an increased risk of osteoporosis or fracture in patients with T2DM.

Effects of Co-administration of Sulfonylureas and Antimicrobial Drugs on Hypoglycemia in Patients with Type 2 Diabetes Using a Case-Crossover Design.

OBJECTIVES: The purpose of this study was to investigate the effect of sulfonylureas (SUs) and antimicrobial co-administration on hypoglycemia in patients with type 2 diabetes mellitus (T2DM). METHODS: We conducted a case-crossover study using the Korean Health Insurance Review and Assessment Service-National Inpatient Sample database, using data from 2014 to 2016. Hospitalized adult patients with T2DM who were diagnosed with hypoglycemia and prescribed SUs for at least 120 days were included. Different risk ratings of severity of drug-drug interactions were considered, including "level X, D, or C" in Lexi-Interact online and "contraindicated, major, or moderate" in Micromedex. Exposure to antimicrobials in the 30-day period before the first hypoglycemia diagnosis was assessed. Two control periods (61-90 and 91-120 days) were matched before the diagnosis date. Conditional logistic regression analysis was conducted to compare the odds of antimicrobial exposure. RESULTS: A total of 9339 patients were included. The mean age of the patients was 71.3 ± 10.6 years, and 4818 (51.6%) were women. An increased risk of hypoglycemia was associated with co-administration of SUs and certain antimicrobials (adjusted odds ratio [aOR] 2.56, 95% confidence interval [CI] 2.34-2.80). The antimicrobial agents that were associated with an increased risk of hypoglycemia, when co-administered with SUs, were sulfonamides (aOR 2.99, 95% CI 1.99-4.52), fluoroquinolones (aOR 2.62, 95% CI 2.38-2.89), macrolides (aOR 2.48, 95% CI 1.88-3.27), and tetracyclines (aOR 1.56, 95% CI 1.05-2.33). CONCLUSIONS: Co-administration with SUs and certain antimicrobials increased the risk of hypoglycemia. Thus, clinically relevant interactions in patients concurrently using SUs and antimicrobials should be monitored, especially within 30 days after co-administration.

Adverse events and concurrent medications associated with parenteral nutrition use.

In this study, clinical manifestations of adverse events and frequently used medications in patients receiving parenteral nutrition (PN) in Korea were evaluated using Korea Adverse Event Reporting System (KAERS) database records between 2011 and 2015. Amino acids, fat emulsions, carbohydrates, combinations and solutions for PN were identified as causative agents. Adverse events classified as "certain", "probable" and "possible" based on the WHO-Uppsala Monitoring Centre criteria were analysed. In total, 6439 adverse events from 4260 patients were included for analysis. Mean patient age was 54.4 ± 18.1 years and the mean number of adverse events per patient was 1.5 ± 1.1. Frequent adverse events were gastrointestinal (2159 events, 33.5%), skin/appendage (1344 events, 20.9%), general (846 events, 13.1%) and central/peripheral nervous system (716 events, 11.1%) disorders. Common clinical symptoms were nausea (1248 events, 19.4%), vomiting (558, 8.7%), pruritus (456 events, 7.1%), rash (386 events, 6.0%) and dizziness (329 events, 5.1%). The frequently reported concomitant agents were tramadol (n = 475, 3.1%), fentanyl (n = 405, 2.7%), paracetamol (n = 329, 2.2%), ketorolac (n = 322, 2.1%) and metoclopramide (n = 289 cases, 1.9%). The frequent adverse events remained consistent after accounting for concurrent medications. Our findings from a nationwide reporting system database found that gastrointestinal disorders (nausea and vomiting) were the leading adverse events, requiring further studies on their prevalence, mechanisms and therapeutic options.