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Q In patients with diabetes, what is the relative efficacy, safety, and acceptability of inhaled insulin compared with subcutaneous (SC) insulin and oral hypoglycaemic agents?
Medline (June 2006), Cochrane Controlled Clinical Trials Register (Issue 2, 2006), reference lists, and the US Food and Drug Administration web site.
Study selection and assessment:
English language randomised controlled trials (RCTs) that compared inhaled insulin with SC insulin or oral hypoglycaemic agents in non-pregnant adults with type 1 or type 2 diabetes and had a duration ⩾12 weeks. 16 RCTs (n = 4023, mean age range 29–60 y, 58% men) met the selection criteria. Methodological quality was assessed based on randomisation method, intention to treat analysis, dropout rate, and primary outcome (efficacy or safety).
change in haemoglobin A1c (HbA1c) concentration, proportion of patients achieving HbA1c concentrations <7%, severe hypoglycaemia, cough, change in pulmonary function, and weight change.
Inhaled insulin did not reduce HbA1c concentrations as much as SC insulin in patients with type 1 and type 2 diabetes but reduced it more than oral agents in patients with type 2 diabetes (table⇓). The proportions of patients who achieved HbA1c concentrations <7% or had ⩾1 episode of severe hypoglycaemia did not differ between inhaled and SC insulin but were higher with inhaled insulin than with oral agents (table⇓). Weight gain did not differ between inhaled and SC insulin (7 RCTs) but was higher with inhaled insulin than with combination oral therapy (3 RCTs). Risks of adverse pulmonary outcomes (cough and decreased FEV1 [15 RCTs]) were greater with inhaled insulin than with the other treatments. Patients with type 1 diabetes had greater decreases in diffusing capacity of carbon monoxide with inhaled insulin than with SC insulin (6 RCTs).
In patients with diabetes, inhaled insulin provides better glycaemic control than oral hypoglycaemic agents but not subcutaneous insulin. Inhaled insulin increases hypoglycaemia more than oral agents and increases pulmonary side effects more than other treatment modalities.
A modified version of this abstract appears in Evidence-Based Medicine and ACP Journal Club.
Achieving optimal glycaemic control (HbA1c <7%) with minimal side effects is the goal for patients with diabetes, albeit a goal achieved by <50% of North American adults with diabetes.1 Although insulin is an effective treatment option, reluctance to initiate SC injections is common2 and has driven the search for alternative treatments.
The meta-analysis by Ceglia et al included relevant trials on inhaled insulin published in the past 40 years. Although data from 16 trials were included in the analysis (all funded by pharmaceutical companies), the long term ramifications and potential pulmonary toxicity of inhaled insulin could not be determined because most studies were conducted over ⩽6 months. In addition, the ability to assess the effects of inhaled insulin by race or ethnicity could not be established because most patients were Caucasian. However, with recent US Food and Drug Administration approval for inhaled insulin and positive patient reports of comfort, ease of administration, and improvement in quality of life, patient requests for this route of delivery are likely to increase.
Clearly, data on long term administration of inhaled insulin are required to evaluate fully its effect on pulmonary function. Despite the lack of long term safety and efficacy data, inhaled insulin may be clinically useful at present for needle-phobic patients who would refuse insulin injections or patients with lipodystrophy who would benefit from a short term break or reduction in insulin injections.
For correspondence: Drs A G Pittas or L Ceglia, Tufts-New England Medical Center, Boston, MA, USA.;
Sources of funding: National Institutes of Health and Friedman New York Foundation for Medical Research.
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