A randomized controlled assessment of the effects of different dosing regimens of budesonide on the HPA-axis in healthy subjects

Aims To investigate the effect on the hypothalamo-pituitary-adrenal (HPA) axis of treatment with budesonide, 400 mg once daily, morning or evening, or 200 mg twice daily, and 800 mg twice daily via Turbuhaler in a randomized, placebo-controlled, double-blind, double-dummy crossover study. Methods Healthy men received budesonide, 400 mg in the morning (08.00±09.00 h) or evening (20.00±21.00 h), budesonide, 200 mg twice daily, 800 mg twice daily, and placebo twice daily, for 1 week each. Plasma and urine samples were obtained over 24 h on day 7 for cortisol determination. Twenty-®ve subjects completed all treatments, and 27 were included in the analysis. Results The 24 h plasma cortisol concentrations vs placebo (95% CI) were 98% (89, 108) for 400 mg in the morning, 92% (83, 100) for 400 mg in the evening, 95% (86, 104) for 200 mg twice daily, and 76% (70, 84) for 800 mg twice daily. Conclusions Budesonide at a dose of 400 mg day x1 via Turbuhaler had no statistically signi®cant effect on 24 h cortisol production, irrespective of whether treatment is given once or twice daily, whereas a dose of 800 mg twice daily resulted in a statistically signi®cant suppression vs placebo. Neither could a signi®cant difference be found between morning and evening dosing

The cost-effectiveness of exenatide twice daily (BID) vs insulin lispro three times daily (TID) as add-on therapy to titrated insulin glargine in patients with type 2 diabetes

Objective: To evaluate the cost-effectiveness of exenatide twice daily (BID) vs bolus insulin lispro three times daily (TID) as add-on therapy when glycemic control is sub-optimal with titrated basal insulin glargine and metformin. Methods: The analysis was based on the recent 4B Study, which compared exenatide BID and lispro TID as add-on therapies in subjects with type 2 diabetes insufficiently controlled, despite titrated insulin glargine. The Cardiff Diabetes Model was used to simulate patient costs and health benefits beyond the 4B Study. The Swedish healthcare perspective was adopted for this analysis; costs are reported in €EUR to aid interpretation. The main outcome measure was the cost per quality-adjusted life-year (QALY) gained with exenatide BID compared to lispro TID. Results: Exenatide BID was associated with an incremental cost of €1,270 and a QALY increase of +0.64 compared with lispro TID over 40 years. The cost per QALY gained with exenatide BID compared with lispro TID was €1,971, which is within conventional limits of cost-effectiveness. Cost-effectiveness results were generally robust to alternative assumptions and values for key model parameters. Limitations: Extrapolation of trial data over the longer term can be influenced by modeling and parameter uncertainty. Cost-effectiveness results were generally insensitive to alternative values of key model input parameters and across scenarios. Conclusions: The addition of exenatide BID rather than insulin lispro to basal insulin is associated with similar or better clinical outcomes. Illustrated from the Swedish healthcare perspective, analysis with the Cardiff Diabetes Model demonstrated that exenatide BID represents a cost-effective treatment alternative to lispro TID as add-on therapy in type 2 diabetes patients insufficiently controlled on basal insulin

CCDC 2190057: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures