Incidence of urinary tract infection in patients with type 2 diabetes. Experience from adverse event reporting in clinical trials.

PURPOSE: Diabetes mellitus has long been widely considered to be associated with an increased risk of urinary tract infection (UTI), but information on incidence rates are scarce and risk factor data have been conflicting. The aim was to estimate UTI incidence and evaluate potential risk factors for UTI in patients with type 2 diabetes included in recent clinical trials. METHODS: Type 2 diabetes patients from 10 AstraZeneca phase III diabetes clinical trials (n=6016, mean 57.4 years, 50.7% female) conducted during 2004-2007 were included. Patients free of UTI at baseline were followed for up to 6 months after inclusion in the trials. UTI was considered present if any term sorting under the MedDRA high-level term "UTIs" was recorded as an adverse event. RESULTS: In all, 142 patients had an adverse event for UTI, corresponding to an incidence of 59.5/1000 person-years for all patients (91.5/1000 in women, 28.2/1000 in men) and a cumulative incidence of 2% during 6 months. Female gender was associated with an increased incidence [relative risk (RR) 3.4; 95% confidence interval (CI) 2.3-5.1] and also higher age (RR 2.5 [95% CI 1.4-4.8] for ages ≥ 70 years vs. 40-49 years). No increased incidence was associated with body mass index (25-29, 30+ vs. <25 kg/m(2) ), HbA1c (<8% vs. >8%), race (Black, Oriental vs. Caucasian) or drug treatment (study drug, comparator vs. placebo). A history of immune system disorder conveyed a twofold higher risk for UTI. CONCLUSION: UTI is common among female patients with type 2 diabetes and older patients of both genders.

Occurrence of community-acquired respiratory tract infection in patients receiving esomeprazole: retrospective analysis of adverse events in 31 clinical trials.

BACKGROUND: A potential causal association between an increase in gastric pH and a risk of community-acquired respiratory tract infection (RTI), specifically pneumonia, has been debated in relation to the use of potent gastric acid-suppressive medication. OBJECTIVE: To investigate the occurrence of community-acquired RTI, including pneumonia, in patients receiving esomeprazole versus placebo and other acid-suppressive agents in randomized clinical trials. METHODS: The AstraZeneca ARIADNE safety database was searched for comparative, controlled phase II-IV randomized, blinded clinical studies with esomeprazole and standard reporting of all adverse events (AEs). Pooled AE data were presented according to treatment comparison (esomeprazole versus placebo, esomeprazole 40 mg versus 20 mg daily, esomeprazole versus omeprazole, lansoprazole and/or ranitidine, respectively). Frequency and relative risk (RR), with 99% confidence interval (CI) and adjustment for time on treatment, were calculated for the following four AE categories: all RTIs; signs and symptoms potentially indicating RTI; lower RTI; and pneumonia. RESULTS: Thirty-one studies were identified, in which 16 583 patients received esomeprazole and 12 044 patients received either placebo or comparator acid-suppressive drugs. The occurrence of all four categories of AEs was similar between esomeprazole and placebo (all RTIs: 9.2% versus 8.5%; signs and symptoms of RTI: 1.8% versus 1.8%; lower RTI: 1.6% versus 1.5%; and pneumonia: 0.2% in both groups). The RR estimates were as follows: all RTIs, 0.93 (99% CI 0.78, 1.11); signs and symptoms of RTI, 0.85 (99% CI 0.57, 1.27); lower RTI, 0.92 (99% CI 0.59, 1.42); and pneumonia, 0.94 (99% CI 0.29, 3.07). The distribution of RTIs by patient sex and age showed a similar pattern in esomeprazole and placebo-treated patients. The comparisons of esomeprazole with the other comparator acid-suppressive drugs showed a similar pattern with only minor numerical differences in the occurrence of RTI between the drugs. There were no significant between-group differences with esomeprazole versus placebo for all four categories of AEs according to esomeprazole dosage, treatment indication and duration of treatment. CONCLUSIONS: This pooled analysis found no causal association between acid-suppressive therapy with esomeprazole and increased risk of community-acquired RTI, including pneumonia, in patients receiving this agent for gastric acid-related disorders.