• P Royle, N Waugh, L McAuley, L McIntyre, and S Thomas.
• Cochrane Db Syst Rev. 2004 Jan 1(3):CD003890.

BackgroundInsulin therapy often relies on multiple daily injections of insulin. However this is a considerable burden to many people with diabetes and adherence to such an insulin regimen can be difficult to maintain, hence compromising optimal glycaemic control. Also, short acting injected insulin is absorbed more slowly than insulin released by the normal pancreas in response to a meal. Inhaled insulin has the potential to reduce the number of injections to perhaps one long-acting insulin per day, and provide a closer match to the natural state, by more rapid absorption from the lung.ObjectivesTo compare the efficacy, adverse effects and patient acceptability of inhaled versus injected insulin.Search StrategyA sensitive search strategy for randomised controlled or cross-over trials was combined with key terms for inhaled insulins. Databases searched were: The Cochrane Library, MEDLINE, PubMed, EMBASE, Science Citation Index, BIOSIS, Web of Science Proceedings, National Research Register UK, Current Controlled Trials, ClinicalTrials.gov, Conference Papers Index, LexisNexis, and web sites of the ADA and EASD were searched for recent meeting abstracts. Reference lists and journals were handsearched. There were no language restrictions on searching. Manufacturers of inhaled insulin were also contacted. Date of last search October 2002.Selection CriteriaOnly randomised controlled trials with parallel groups or controlled cross-over trials, including type 1 or type 2 diabetic patients of any age treated with insulin, were considered eligible. The minimum trial duration considered was 10 weeks, as this is the time taken for glycated haemoglobin to reliably reflect changes in glycaemic control.Data Collection And AnalysisTrial selection and evaluation of study quality was performed independently by two reviewers. The quality of reporting of each trial was assessed according to a modification of the criteria outlined in Centre for Reviews and Dissemination (CRD) Report 4, Spitzer; and Jadad.Main ResultsSix randomised controlled trials were found and the overall number of participants was 1191. Three trials included patients with type 1 diabetes and three with type 2 diabetes. Three trials had a duration of 24 weeks, and three of 12 weeks. All were open label. There was insufficient information to determine the study quality. Results for HbA1c were similar for all trials, in that all showed comparable glycaemic control for inhaled insulin compared to an entirely subcutaneous regimen. All trials that reported patient satisfaction and quality of life showed that these were significantly greater in the inhaled insulin group. Overall there was no difference in total hypoglycaemic episodes between the groups, but one trial showed a statistically significant increase in severe hypoglycaemic episodes for the inhaled insulin group. No adverse pulmonary effects were observed in any of the studies, but longer follow-up will be required to be sure that there are no adverse side-effects. Cavets include: few studies published in full (so quality could not be assessed), and only two studies used the same basal regimen in both the inhaled and injected groups.Reviewers' ConclusionsInhaled insulin taken before meals, in conjunction with an injected basal insulin, has been shown to maintain glycaemic control comparable to that of patients taking multiple daily injections. The key benefit appears to be that patient satisfaction and quality of life are significantly improved, presumably due to the reduced number of daily injections required. However, the patient satisfaction data is based on five trials, of which only two have been published in full; also the three trials containing quality of life data are all only published in abstract form at present. In addition, longer term pulmonary safety data are still needed. Also, the lower bioavailability, and hence higher doses of inhaled insulin required, may make it less cost-effective than injected insulin.

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