Background:The benefits of pharmacotherapy with tiotropium HandiHaler 18 μg for patients with chronic obstructive pulmonary disease (COPD) have been previously demonstrated. However, few data exist regarding the treatment of moderate disease (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II).Aims:To determine whether tiotropium improves lung function/patient-reported outcomes in patients with GOLD stage II COPD naive to maintenance therapy.Methods:A randomised 24-week double-blind placebo-controlled trial of tiotropium 18 μg once daily (via HandiHaler) was performed in maintenance therapy–naive patients with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7 and post-bronchodilator FEV1 ⩾50 and <80%.Results:A total of 457 patients were randomised (238 tiotropium, 219 placebo; mean age 62 years; FEV1 1.93 l (66% predicted)). Tiotropium was superior to placebo in mean change from baseline in post-dose FEV1 area under the curve from 0 to 3 h (AUC0–3h) at week 24 (primary endpoint): 0.19 vs. −0.03 l (least-squares mean difference 0.23 l, P<0.001). FVC AUC0–3h, trough and peak FEV1 and FVC were significantly improved with tiotropium versus placebo (P<0.001). Compared with placebo, tiotropium provided numerical improvements in physical activity (P=NS). Physician’s Global Assessment (health status) improved (P=0.045) with less impairment on the Work Productivity and Activity Impairment questionnaire (P=0.043) at week 24. The incidence of exacerbations, cough, bronchitis and dyspnoea was lower with tiotropium than placebo.Conclusions:Tiotropium improved lung function and patient-reported outcomes in maintenance therapy–naive patients with GOLD stage II COPD, suggesting benefits in initiating maintenance therapy early.

OBJECTIVE -The purpose of this study was to evaluate the long-term (2-year) safety and efficacy of inhaled human insulin (Exubera [insulin human (rDNA origin)] inhalation powder) (EXU) in adult patients with type 1 diabetes. , indicating that the significant difference between the treatment groups in FEV 1 developed during the first 3 months and was not progressive thereafter. Adverse event profiles were similar except for a higher incidence of cough (usually mild and unproductive) in patients receiving EXU (37.6 vs. 13.1%) that decreased to 1.3% by month 24. Glycemic control was sustained in both groups (adjusted mean treatment difference in change from baseline A1C at month 24 0.25 Ϯ 0.07% [0.13-0.37]). Although the overall hypoglycemic events were comparable between groups (4.0 vs. 3.8 events/subject-month), the incidence of severe hypoglycemic events was lower with EXU than with SC insulin (2.8 vs. 4.1 events/100 subject-months, risk ratio 0. RESEARCH DESIGN AND METHODS

Three double‐blind, placebo‐controlled, three‐parallel‐group, multicenter phase 3 trials were conducted to assess the efficacy and safety of CP‐945,598 for weight loss and weight‐loss maintenance. Two trials were designed to be 2 years in duration (in obese and overweight patients) and one as a 1‐year study (in obese and overweight patients with type 2 diabetes). However, the 2‐year trials and the CP‐945,598 development program were terminated before completion due to changing regulatory perspectives of CB1 receptor‐related drugs. In total, 1,253 and 2,536 participants in the two 2‐year multinational and North American studies were randomized to 10‐mg CP‐945,598 (n = 360; 718); 20‐mg CP‐945,598 (n = 534, 1,084) and placebo (n = 359, 734), respectively; and 975 participants were randomized to 10‐mg CP‐945,598 (n = 318); 20‐mg CP‐945,598 (n = 320); and placebo (n = 337) in the 1‐year multinational diabetes trial. Baseline demographics were similar between treatment groups within each trial. One year of treatment with CP‐945,598 resulted in a dose‐related mean percentage reduction from baseline body‐weight in all trials. A significant proportion of all participants also achieved 5% and 10% weight loss after 1 year. In participants with mainly well‐controlled type 2 diabetes, the combination of lifestyle and CP‐945,598 induced substantial improvements in glycemic control. The most frequent adverse events (AEs) for CP‐945,598 were: diarrhea, nausea, nasopharyngitis, and headache. Self‐reported experiences of anxiety and suicidal thoughts were higher with CP‐945,598 than placebo, as were the incidence of depression and depressed mood. However, the reported increases in psychiatric symptoms were not consistently dose dependent.

OBJECTIVE -The purpose of this study was to evaluate the 2-year pulmonary safety of inhaled human insulin (Exubera [EXU]) in 635 nonsmoking adults with type 2 diabetes.RESEARCH DESIGN AND METHODS -Patients were randomly assigned to receive prandial EXU or subcutaneous insulin (regular or short-acting) plus basal (intermediate-or long-acting) insulin. The primary end points were the annual rate of decline in forced expiratory volume in 1 s (FEV 1 ) and carbon monoxide diffusing capacity (DL CO ).RESULTS -Small differences in FEV 1 favoring subcutaneous insulin developed during the first 3 months but did not progress. Adjusted treatment group differences in FEV 1 annual rate of change were Ϫ0.007 l/year (90% CI Ϫ0.021 to 0.006) between months 0 and 24 and 0.000 l/year (Ϫ0.016 to 0.016) during months 3-24. Treatment group differences in DL CO annual rate of change were not significant. Both groups sustained similar reductions in A1C by month 24 (last observation carried forward) (EXU 7.7-7.3% vs. subcutaneous insulin 7.8 -7.3%). Reductions in fasting plasma glucose (FPG) were greater with EXU than with subcutaneous insulin (adjusted mean treatment difference Ϫ12.4 mg/dl [90% CI Ϫ19.7 to Ϫ5.0]). Incidence of hypoglycemia was comparable in both groups. Weight increased less with EXU than with subcutaneous insulin (Ϫ1.3 kg [Ϫ1.9 to Ϫ0.7]). Adverse events were comparable, except for a higher incidence of mild cough and dyspnea with EXU.CONCLUSIONS -Two-year prandial EXU therapy showed a small nonprogressive difference in FEV 1 and comparable sustained A1C improvement but lower FPG levels and less weight gain than seen in association with subcutaneous insulin in adults with type 2 diabetes.

SummaryObjectiveHigh‐attrition rates have been observed in long‐term clinical trials of weight loss agents. We evaluated the impact of an innovative retention programme on 1‐year retention.MethodsThree Phase 3 global multicentre clinical trials evaluated the efficacy and safety of a CB1 receptor antagonist in subjects with BMI ≥ or = 27 kg/m2. The impact of a multifaceted retention programme including a dietitian screening interview, a comprehensive culturally adapted lifestyle modification programme, and a dietitian support system to maximize lifestyle adherence, was evaluated in 4,410 subjects from four subpopulations (non‐US English‐speaking, non‐English‐speaking, US‐without dietitian screening and US‐with dietitian screening) comprising 208 centres from 15 countries.ResultsThe median proportion retained over the first year among subjects in three protocols was 82%. Non‐English‐speaking countries showed higher retention rates (89%) compared with the USA (73%) and non‐US English‐speaking (81%) countries. Within the USA, behavioural screening was associated with 29% reduction in dropout rate; for every five monthly teleconferences attended above 11, there was a 32% decrease in dropout rate.ConclusionsThis novel retention programme greatly improved upon reported retention rates of studies conducted with other weight loss agents in long‐term clinical trials. Its effectiveness should be confirmed in future trials.