Subcutaneous rapid-acting insulin analogues in mild to moderate diabetic ketoacidosis: A meta-analysis of randomized controlled trials

Introduction: Diabetic Ketoacidosis (DKA) is commonly treated with intravenous (IV) regular insulin. However, patients with less severe DKA may benefit from a subcutaneous (SC) scheme. Methods: We systematically searched PubMed, Cochrane, and Embase for randomized controlled trials (RCTs) comparing SC rapid-acting insulin analogue (RAIAs) with IV regular insulin. Risk ratios (RR) were used to compare treatment effects for binary outcomes and mean differences (MD) for continuous data with the corresponding 95 % confidence intervals (CI). P values <0.05 were considered statistically significant. We used the R version 4.3.2 for statistical analyses. Results: Our meta-analysis included eight RCTs encompassing 415 patients. No statistically significant differences were found between RAIAs and IV regular insulin in the treatment of mild to moderate DKA in the pediatric and adult population in the primary outcome of time until DKA resolution (MD 0.00 h; 95 % CI -1.27 to 1.28; P = 1.00). Both treatments showed comparable results in the secondary outcomes total insulin usage (P = 0.65), time until hyperglycemia resolution (P = 0.22), length of hospital stay (P = 0.11), the incidence of hypoglycemia (P = 0.15) and DKA recurrence (P = Not estimable). There were no reports of death, cerebral edema, or venous thrombosis in the studies. Conclusion: In this meta-analysis of eight RCTs we found that SC RAIAs and regular IV insulin are comparable in resolving mild to moderate DKA in children and adults. PROSPERO registration: CRD42023485032.