B. Nguyen, S. Quon, B. Dhaliwal, M. Warwas and S. Stafford (2026). Early versus late initiation of long-acting insulin in paediatric and adult diabetic ketoacidosis: A systematic review and meta-analysis of randomised control trials. Diabetes, obesity & metabolism, 28(5), 3655-3663. https://doi.org/10.1111/dom.70542

PubMed 41657118

[Abstract]
AIMS: Diabetic ketoacidosis (DKA) is a serious complication of diabetes, requiring intravenous (IV) insulin until resolution and subsequent transition to subcutaneous insulin. Currently, clinical guidelines vary regarding the timing of long-acting subcutaneous insulin initiation, with some advocating early administration during IV insulin infusion, while others recommend delaying until DKA resolution. We aimed to evaluate the efficacy and safety of concurrent versus sequential initiation of long-acting subcutaneous insulin in paediatric and adult patients with DKA already receiving regular insulin.

MATERIALS AND METHODS: A systematic search of five databases (inception to January 2026) identified eligible studies. Early initiation was defined as administration of long-acting insulin before resolution of DKA, while late initiation occurred after resolution of DKA. Primary outcomes included time to DKA resolution, total IV insulin and fluid requirements, and risks of hypoglycaemia, hypokalaemia, and rebound hyperglycaemia. Pooled effect sizes were calculated using random-effects models.

RESULTS: Nine randomised control trials encompassing 652 patients were included. Early long-acting insulin was associated with a shorter time to DKA resolution (SMD: -0.61; 95% CI: -0.83 to -0.38) and was associated with lower total insulin and fluid requirements. Available evidence was insufficient to rule out an increased risk of hypoglycaemia (RR: 0.81; 95% CI: 0.52-1.27) or hypokalaemia (RR: 1.21; 95% CI: 0.90-1.63).

CONCLUSIONS: Early initiation of long-acting insulin during IV insulin infusion in DKA likely shortens time to resolution based on moderate certainty evidence and may reduce total insulin and fluid requirements. Evidence for rebound hyperglycaemia and recurrent DKA outcomes remains limited and imprecise.