Title : Efficacy and safety of inhaled versus subcutaneous insulin in type 1 and type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials
Abstract:
Background: Inhaled insulin offers a non-invasive alternative to subcutaneous (SC) insulin and may improve adherence in patients with diabetes mellitus. However, its comparative efficacy, safety, and impact on pulmonary function remain unclear.
Methods: We systematically searched PubMed, Embase, Cochrane Central, and Web of Science (January 2000–January 2025) for randomized controlled trials comparing inhaled and SC insulin in type 1 or type 2 diabetes. Inclusion criteria required ≥12-week duration and reporting of at least one prespecified outcome. Primary outcomes were changes in glycated hemoglobin (HbA1c) and fasting blood glucose (FBG). Secondary outcomes included body weight, hypoglycemia, adverse events, pulmonary function (FEV₁, DLCO), and proportion achieving HbA1c <7%. Risk of bias was assessed with the Cochrane RoB-2 tool. Pooled mean differences (MD) and risk ratios (RR) were calculated using random-effects models in RevMan 5.4, with subgroup and sensitivity analyses by diabetes type.
Results: Nineteen RCTs involving 5,879 participants were included. Inhaled insulin achieved greater FBG reduction than SC insulin (MD = –22.12 mg/dL; 95% CI: –29.29, –14.95; p < 0.00001) but was associated with a modestly smaller HbA1c reduction (MD = 0.14%; 95% CI: 0.07, 0.21; p < 0.00001). Weight gain was significantly lower with inhaled insulin (MD = –1.18 kg; 95% CI: –1.44, –0.93; p < 0.00001). No significant differences were observed in hypoglycemia risk (RR = 0.97; p = 0.22), adverse events (RR = 1.02; p = 0.17), or HbA1c <7% achievement (RR = 0.96; p = 0.71). Inhaled insulin caused small but significant declines in DLCO (MD = –0.44; p = 0.01) and FEV₁ (MD = –0.03 L; p < 0.00001), primarily in type 1 diabetes.
Conclusion: Inhaled insulin provides superior fasting glucose control and less weight gain compared with SC insulin, without increasing hypoglycemia or adverse events. However, modest HbA1c differences and pulmonary function declines warrant careful patient selection and routine lung monitoring.
Keywords: inhaled insulin, subcutaneous insulin, diabetes mellitus, meta-analysis, pulmonary function
