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

Introduction:Current smoking cessation guidelines recommend setting a quit date prior to starting pharmacotherapy. However, providing flexibility in the date of quitting may be more acceptable to some smokers. The objective of this study was to compare varenicline 1 mg twice daily (b.i.d.) with placebo in subjects using a flexible quit date paradigm after starting medication.Methods:In this double-blind, randomized, placebo-controlled international study, smokers of ≥10 cigarettes/day, aged 18–75 years, and who were motivated to quit were randomized (3:1) to receive varenicline 1 mg b.i.d. or placebo for 12 weeks. Subjects were followed up through Week 24. Subjects were instructed to quit between Days 8 and 35 after starting medication. The primary endpoint was carbon monoxide–confirmed continuous abstinence during Weeks 9–12, and a key secondary endpoint was continuous abstinence during Weeks 9–24.Results:Overall, 493 subjects were randomized to varenicline and 166 to placebo. Continuous abstinence was higher for varenicline than for placebo subjects at the end of treatment (Weeks 9–12: 53.1% vs. 19.3%; odds ratio [OR] 5.9; 95% CI, 3.7–9.4; p < .0001) and through 24 weeks follow-up (Weeks 9–24: 34.7% vs. 12.7%; OR 4.4; 95% CI, 2.6–7.5; p < .0001). Serious adverse events occurred in 1.2% varenicline (none were psychiatric) and 0.6% placebo subjects. Fewer varenicline than placebo subjects reported depression-related adverse events (2.3% vs. 6.7%, respectively).Conclusions:Varenicline 1 mg b.i.d. using a flexible quit date paradigm had similar efficacy and safety compared with previous fixed quit date studies.

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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.

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