Effects of liraglutide on gallbladder emptying: A randomized, placebo-controlled trial in adults with overweight or obesity.

AIMS: Treatment with liraglutide 3.0 mg has been associated with gallbladder-related adverse events. To conduct a single-centre, double-blind, 12-week trial comparing the effect of 0.6 mg liraglutide and steady-state liraglutide 3.0 mg with placebo on gallbladder emptying in adults with body mass index (BMI) ≥27 kg/m2 and without diabetes. METHODS: Participants were randomized 1:1 to once-daily subcutaneous liraglutide (n = 26) or placebo (n = 26), starting at 0.6 mg with 0.6-mg weekly increments to 3.0 mg, with nutritional and physical activity counselling. A 600-kcal (23.7 g fat) liquid meal test was performed at baseline, after the first dose and after 12 weeks. The primary endpoint was the 12-week maximum postprandial gallbladder ejection fraction (GBEFmax ), measured over 240 minutes after starting the meal. RESULTS: Baseline characteristics were similar between groups (mean ± SD overall age 47.6 ± 10.0 years, BMI 32.6 ±3.4 kg/m2 , 50% women). Mean 12-week GBEFmax (treatment difference -3.7%, 95% confidence interval [CI] -13.1, 5.7) and area under the GBEF curve in the first 60 minutes (-390% × min, 95% CI -919, 140) did not differ for liraglutide 3.0 mg (n = 23) vs placebo (n = 24). The median (range) time to GBEFmax was 151 (11-240) minutes with liraglutide 3.0 mg and 77 (22-212) minutes with placebo. Similar findings were noted after the first 0.6-mg liraglutide dose. Gastrointestinal disorders, notably nausea and constipation, were the most frequently reported adverse events. CONCLUSIONS: Treatment with liraglutide did not affect the GBEFmax but appeared to prolong the time to GBEFmax .

Depression and the risk of severe infections: prospective analyses on a nationwide representative sample.

BACKGROUND: Preliminary research suggests an association between depression and subsequent increased risk of infections, yet little is known on this topic. This study investigated the association between depression and risk of various types of infections, including temporal and dose-response relationships. METHODS: A prospective population-based study including 976,398 individuals, of whom 142,169 had a history of depression between 1995 and 2012, was conducted using linked Danish registries. Survival analyses were used to estimate the relative risk of infections among those with depression, compared with those without depression, while adjusting for gender and age. RESULTS: Depression was associated with increased risk of a wide range of infections [incidence rate ratio (IRR) = 1.61, 95% confidence interval (CI) = 1.49-1.74, P = 0.000, for any infection]. There was no evidence of a specific temporal effect but rather a general increased risk of infection subsequent to the onset of depression, as the risk during first year (IRR = 1.67, 95% CI = 1.25-2.22, P = 0.000) remained elevated for the ensuing 11 years and beyond (IRR = 1.61, 95% CI = 1.39-1.85, P = 0.000). Dose-response analyses revealed that the risk of infection increased by 59% (IRR = 1.59, 95% CI = 1.45-1.75, P = 0.000) following a single depressive episode and was elevated even further (IRR = 1.97, 95% CI = 0.92-4.22, P = 0.082) following four or more depressive episodes. However, results did not indicate a perfect linear association. CONCLUSIONS: Findings suggest the presence of depression may confer an increased risk of infection and that this increased susceptibility is not confined to a specific time period following the onset of depression. A dose-response relationship may be present, but more research is needed to further examine and confirm a link between depression and risk of infection.