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.
| Specialty | Score |
|---|---|
| Hospital Doctor/Hospitalists | |
| Internal Medicine | |
| Endocrine | |
| Emergency Medicine | |
| Pediatric Emergency Medicine | |
| Pediatric Hospital Medicine |
Interesting synthesis of SQ + IV insulin DKA trials but misses an equally important point that mild DKA patients require no IV insulin based on a series of non-randomized observational studies (http://pmid.us/36775281 and http://pmid.us/39308229 and http://pmid.us/39313955).
This meta-analysis including 8 RCTs (468 patients) evaluated subcutaneous basal insulin with IV insulin versus IV insulin alone in adult DKA. The authors found early SC basal insulin reduced time-to-DKA resolution (MD -4.02 hours) and total IV insulin doses until DKA resolved. There were no differences in rebound hyperglycemia, safety, LOS, or mortality. There were limitations including exclusion of those with advanced CKD/ESRD, with heterogeneity among studies, with dated use of definition for DKA resolution. However, this meta-analysis lends important information to DKA management.
This systematic review and meta-analysis on the treatment of diabetic ketoacidosis (DKA) found that early administration of subcutaneous (SC) basal insulin along with standard intravenous insulin infusion significantly accelerates the resolution time of DKA by 4.02 hours. Early use of SC basal insulin reduces the total intravenous insulin dose required by 19.12 units. This supports the idea that early basal insulin helps suppress ketogenesis and accelerate recovery from acidosis. Furthermore, long-acting or ultra-long-acting SC basal insulin did not increase the risk for hypoglycemia or hypokalemia. It can be argued that the administration of long-acting SC insulin along with IV insulin therapy is a safe and effective adjunct.
This systematic review assesses the effectiveness and safety of initiating subcutaneous (SC) basal insulin early, alongside intravenous insulin infusion, compared with using IV insulin infusion alone for treating diabetic ketoacidosis (DKA). The evidence indicates that early SC basal insulin, when combined with IV insulin, speeds up DKA resolution and reduces overall IV insulin needs, without increasing the risk of adverse events such as hypoglycemia or hypokalemia.
This article is interesting but should be read with caution as it did not involve patients under the age of 12. DKA in the paediatric population is associated with higher rates of cerebral oedema and other complications, so studies are needed for this age group.
, McMaster University