Efficacy, safety, and patient acceptability of Technosphere inhaled insulin for people with diabetes: a systematic review and meta-analysis

Background Technosphere inhaled insulin is a non-invasive alternative to subcutaneous injectable insulin for adults with type 1 or 2 diabetes. In this systematic review and meta-analysis of randomised controlled trials, we aimed to establish the efficacy, safety, and patient acceptability of Technosphere inhaled insulin in patients with diabetes. Methods We searched MEDLINE, the Cochrane Central Register of Controlled Clinical Trials, ClinicalTrials.gov, and relevant US regulatory documents for reports of randomised trials published in English up to May 30, 2015, that compared mealtime Technosphere inhaled insulin with placebo, subcutaneous insulin, or oral antidiabetic drugs in people with type 1 or type 2 diabetes. Two reviewers independently extracted data for outcomes of interest and risk of bias. Endpoints included changes in HbA(1c) concentration and bodyweight, and safety outcomes, including severe hypoglycaemia and pulmonary toxicity. When three or more studies provided relevant data, we did a meta-analysis for the outcome using a profile-likelihood random-effects model. Findings 13 trials met the inclusion criteria for qualitative systematic review; 12 met the inclusion criteria for quantitative meta-analysis (n=5273; age range 18-80). HbA(1c) decrease from baseline was greater with subcutaneous insulin than with Technosphere inhaled insulin (net difference 0.16%, 95% CI 0.06-0.25; eight trials). However, inhaled insulin was associated with less weight gain (net difference -1.1 kg, -2.1 to -1.6; three trials) and a smaller risk of severe hypoglycaemia (odds ratio 0.61, 95% CI 0.35-0.92; five trials). Incidence of mild transient cough was increased in people allocated to inhaled insulin (odds ratio 7.82, 6.14-10.15; seven trials) compared with those allocated to active comparator groups, as was the decrease in forced expiratory volume in 1 s (net difference -0.038 L, -0.049 to -0.026; five trials). Quality of life and overall patient satisfaction did not differ significantly between inhaled insulin groups and active comparator groups (no numerical estimate). Interpretation Glycaemic efficacy of Technosphere inhaled insulin is lower than that of subcutaneous insulin, but inhaled insulin has a lower risk of severe hypoglycaemia and weight gain. Long-term outcomes and safety with Technosphere insulin should be further investigated. Until further data for safety become available, Technosphere inhaled insulin should be reserved for healthy adults with diabetes who do not have pulmonary disease and who would otherwise delay initiating or intensifying insulin therapy because they are unwilling or unable to use injectable insulin.