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Objective To examine the dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma.

The aim was to determine the effects of dulaglutide, a synthetic once-weekly, injectable human glucagon-like peptide 1 analogue that lowers blood glucose, body weight, appetite and blood pressure, on cardiovascular outcomes. People with type 2 diabetes, aged ≥50 years, with glycated haemoglobin (HbA1c) ≤9.5%, and either a previous cardiovascular event, evidence of cardiovascular disease or ≥2 cardiovascular risk factors were randomly allocated to a weekly subcutaneous injection of either dulaglutide (1.5 mg) or placebo and followed within the ongoing Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial every 3 to 6 months. The primary cardiovascular outcome is the first occurrence of the composite of cardiovascular death or non-fatal myocardial infarction or non-fatal stroke. Secondary outcomes include each component of the primary composite cardiovascular outcome, a composite clinical microvascular outcome comprising retinal or renal disease, hospitalization for unstable angina, heart failure requiring hospitalization or an urgent heart failure visit, and all-cause mortality. Follow-up will continue until the accrual of 1200 confirmed primary outcomes. Recruitment of 9901 participants (mean age 66 years, 46% women) occurred in 370 sites located in 24 countries over a period of 2 years. The mean duration of diabetes was 10 years, mean baseline HbA1c was 7.3%, and 31% had prior cardiovascular disease. The REWIND trial's international scope, high proportion of women, high proportion of people without prior cardiovascular disease and inclusion of participants whose mean baseline HbA1c was 7.3% suggests that its cardiovascular and safety findings will be *clinicaltrials.gov: NCT01394952

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The aim of this study was to examine the dose-response relationship of inhaled budesonide in adolescents and adults with asthma.A meta-analysis was carried out on placebo-controlled, randomised clinical trials, presenting data on at least one outcome measure of asthma and using at least two doses of budesonide, delivered by turbuhaler or metered-dose inhalerzspacer twice daily.A total of six studies of 1,435 adolescents and adults, with mild to moderately severe asthma, met the inclusion criteria for the meta-analysis. A negative exponential model indicated that 80% of the benefit at 1,600 mg?day -1 was achieved at doses of y200-400 mg?day -1 and 90% by 300-600 mg?day -1 . Meta-regression with a quadratic term in dose showed that the maximum effect was obtained with doses of y1,000 mg?day -1 . In conclusion, the available published data indicate that, in adolescents and adults with mild to moderate asthma, most of the therapeutic benefit of budesonide delivered by turbuhaler or metered-dose inhalerzspacer is achieved with a dose of y400 mg?day -1 and the maximum effect is achieved at y1,000 mg?day -1 . This conclusion is qualified by the recognition that there is considerable individual variability in the response to inhaled corticosteroids and that the subjects included in this meta-analysis had predominantly mild to moderate asthma. In a recent meta-analysis of the dose-response relationship of fluticasone, it was shown that most of the therapeutic benefit is achieved with doses of 100-250 mg?day -1 , and that the maximum effect is obtained at y500 mg?day -1 in adolescents and adults with asthma [1]. This therapeutic dose range is two-fold lower than that recommended in the international and national consensus guidelines and formularies, and the dose commonly prescribed in clinical practice [2][3][4]. In view of this disparity and in response to the recommendations of the Cochrane Centre [5], the current authors have further investigated the therapeutic dose range of inhaled corticosteroids by undertaking a similar meta-analysis of the doseresponse relationship of budesonide. MethodsA search of Medline was conducted from Jan 1966 to Jan 2003 and of Embase from Jan 1980 to Jan 2003. On Medline, studies were searched using a combination of the keywords "budesonide" and "dose" or "dosage". AstraZeneca, the manufacturer of budesonide, was also asked for details of all relevant studies; no additional studies were identified. No relevant studies published in other languages were found on Medline or Embase. Finally, the reference lists of relevant studies were examined and no other studies were found. Inclusion criteriaTwo people examined each paper9s title and abstract, and then the full paper if necessary. To be included in the primary meta-analysis, studies had to meet all of the following criteria: a double-blind, placebo-controlled, randomised trial involving two or more doses of budesonide, delivered by turbuhaler or metered-dose inhaler (MDI)zspacer device twice daily, in adolescents (agedw12 yrs) or...

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The dose-response relationship of inhaled fluticasone propionate (FP) for adrenal suppression in adults with asthma is not clear.The current authors carried out a systematic review and meta-analysis of placebo-controlled randomised dose-response studies of o4 weeks' duration, which assessed the adrenal effects of FP by cosyntropin stimulation tests in adult asthma. The main outcome measure was the proportion of subjects with adrenal function below the lower limit of the normal range.Five studies, with a total of 732 subjects with asthma, met the inclusion criteria. Data on daily doses .1,000 mg were limited to one study. The proportion of subjects with adrenal function below the lower limit of the normal range on placebo was 3.9%; for a 500-mg per day increase in FP dose the odds of an abnormality increased by 1.38 (95% confidence interval 1.01-1.59). The continuous secondary outcome measures showed an inverse linear relationship with the FP dose up to 2,000 mg?day -1 .In conclusion, for routine prescribing within the established therapeutic dose-response range (50-500 mg?day -1 ), fluticasone propionate has minimal effects on adrenal function. This conclusion is limited by the paucity of long-term studies of daily doses of fluticasone propionate .1,000 mg and by the considerable individual variability in the response.