Early subcutaneous basal insulin with intravenous insulin infusion for diabetic ketoacidosis management: A systematic review and meta-analysis of randomised controlled trials

Abstract

Aims: To evaluate the effectiveness and safety of early initiation of subcutaneous (SC) basal insulin in combination with intravenous insulin infusion (IVII), compared with IVII alone, for the management of diabetic ketoacidosis (DKA). Materials and Methods: A systematic search of PubMed, Embase, Scopus, and the Cochrane Library was conducted to identify randomised controlled trials (RCTs) comparing early initiation of long- or ultra-long-acting basal insulin plus IVII versus IVII alone in DKA management. Studies published up to 6 September 2025, were included. Meta-analysis was performed using mean difference (MD) for continuous outcomes and risk ratio for dichotomous outcomes, both with a 95% confidence interval (CI). The primary outcome was time to DKA resolution. Secondary outcomes included total intravenous insulin use, rebound hyperglycemia, hypoglycemia, hypokalemia, length of hospital stay (LOS), and mortality. A one-stage individual participant data meta-analysis was also conducted when individual-level data were available. Results: Eight RCTs including 468 participants (256 receiving early SC basal insulin plus IVII; 212 receiving IVII alone) were included. Baseline characteristics were comparable across studies. Early SC basal insulin significantly reduced time to DKA resolution (MD −4.02 h, 95%CI −5.52 to −2.52, p <0.001) and total intravenous insulin dose until DKA resolution (MD −19.2 units, 95%CI −28.99 to −9.26, p <0.001). No significant differences were observed between groups for rebound hyperglycemia, safety outcomes, LOS, or in-hospital mortality. Conclusions: Early SC basal insulin in combination with IVII significantly accelerates DKA resolution and reduces total IVII requirements, without increasing the risk of adverse events, including hypoglycemia or hypokalemia.