Inhaled insulin as adjunctive therapy in subjects with type 2 diabetes failing oral agents: a controlled proof‐of‐concept study

Aim:  This controlled proof-of-concept study investigated inhaled insulin (INH) as adjunctive therapy to existing oral antidiabetic agents in subjects with type 2 diabetes. Methods:  Twenty-four subjects with type 2 diabetes [19 men and 5 women, 56.1 ± 6.6 years, body mass index 32.7 ± 4.2 kg/m2, glycosylated haemoglobin (HbA1c) 8.4 ± 0.8% (mean ± s.d.)] inadequately controlled by metformin and/or sulfonylureas were randomized to receive additional therapy with either INH administered preprandially using a metered-dose inhaler (MDI), or insulin glargine (GLA) injected subcutaneously at bedtime for 4 weeks. Both inhaled and injected insulin doses were titrated to predefined blood glucose (BG) targets. Results:  INH and GLA improved metabolic control to a similar extent. Mean daily BG decreased by 2.8 mmol/l in the INH group (p < 0.001) and by 2.4 mmol/l in the GLA group (p < 0.001). Accordingly, fasting BG (−2.7 vs. −3.6 mmol/l for INH vs. GLA), preprandial- and 2-h postprandial BG, HbA1c (−1.23 vs. −1.05%), body weight (−1.9 vs. −2.3 kg) and serum fructosamine were similarly and significantly reduced in both groups (p < 0.05). Triglycerides decreased significantly with INH (−1.15 μmol/l; p < 0.001) but not with GLA [−0.52 μmol/l; not significant (NS)]. Incidence rates of adverse events did not differ significantly, and there were no indications of respiratory tract irritation. Conclusions:  In subjects with type 2 diabetes inadequately controlled by oral agents, preprandial administration of INH delivered by a MDI provided a comparable metabolic control to bedtime GLA and did not show any safety concerns during a 4-week treatment. These results warrant a more extensive investigation of preprandial treatment with INH in longer term studies.