Early versus late initiation of long-acting insulin in paediatric and adult diabetic ketoacidosis: A systematic review and meta-analysis of randomised control trials.

In pediatric DKA, starting long-acting basal insulin during IV insulin administration with an overlap of four hours or more speeds up metabolic resolution by about 3 to 5h without raising the risk of hypoglycemia or hypokalemia. The effects on the duration of IV insulin and LOS are inconsistent. These findings support the use of early basal insulin as a safe transition strategy. Further multicenter pragmatic RCTs with standardized definitions for overlap are needed. • Diabetic ketoacidosis (DKA) in children is a major medical emergency requiring prompt treatment to avoid severe complications, with the standard treatment involving intravenous (IV) insulin administration. • Long-acting basal insulin has been shown in adult populations to hasten recovery from DKA without increasing the risk of hypoglycemia or hypokalemia. • This meta-analysis emphasizes the effects on the pediatric population, providing high-certainty evidence that early initiation of long-acting basal insulin during IV insulin infusion in pediatric DKA significantly reduces the time to DKA resolution. • The study confirms that early basal insulin does not increase the risk of hypoglycemia or hypokalemia, supporting its safety as a transition strategy in pediatric DKA management.

Disclosure: K. Thammakosol: None. M. Jantarapootirat: None. S. Traiwanatham: None. C. Sriphrapradang: None.Background: Previous studies suggest that adding subcutaneous (SC) long-acting insulin glargine U-100 to standard intravenous (IV) insulin infusion during the initial management of diabetic ketoacidosis (DKA) may accelerate DKA resolution and reduce rebound hyperglycemia. Insulin degludec, an ultralong-acting basal insulin, has been shown to provide more stable glucose control and reduced nocturnal hypoglycemia compared to insulin glargine U-100. However, its role in DKA management remains unexplored. Objectives: To determine the effectiveness and safety of the early combination of SC insulin degludec with IV insulin infusion, compared to IV insulin infusion alone, in DKA management. Study Designs and Methods: This prospective, open-label, randomized controlled trial includes 80 adults aged 18 and older who were diagnosed with DKA. Participants were randomized into 2 groups: the intervention group was administered early SC insulin degludec (0.15-0.3 units/kg SC within 3 hours of DKA diagnosis) in addition to the standard IV insulin infusion protocol. The control group was administered only standard DKA treatment. The primary outcome was time to DKA resolution. Other outcomes included rebound hyperglycemia, rebound DKA, hypoglycemia, hypokalemia, length of hospital stay (LOS), and all-cause mortality. Results: A total of 80 patients were enrolled. Both groups were similar in baseline characteristics, 67.5% had type 2 diabetes (T2D). DKA resolution time was significantly faster in the early degludec group by 3.25 hours (7.75 hours, IQR 6.00-9.00 vs. 11.00 hours, IQR 6.25-15.00; P=0.039). The mean capillary blood glucose (CBG) at 72 hours after switching to SC insulin was significantly lower in the early degludec group (213.9±25.8 vs. 240.1±42.0 mg/dL; P=0.012). The incidence of rebound hyperglycemia at 12 hours after bridging to SC insulin, rebound DKA, hypoglycemia, hypokalemia, LOS, and all-cause mortality were similar between the groups. Conclusions: Early administration of SC insulin degludec, combined with IV insulin infusion, accelerated DKA resolution and improved blood glucose levels at 72 hours after discontinuation of IV insulin, without increasing the risk of hypoglycemia, or hypokalemia.Presentation: Saturday, July 12, 2025

Evidence is inconclusive if early administration of subcutaneous (SQ) long-acting insulin (LAI) in management of diabetic ketoacidosis (DKA) improves outcomes. This study compares early versus late administration of SQ LAI in time to DKA resolution. This single-center, retrospective study included patients with DKA who received ≥12 hours of continuous intravenous insulin (CIVI) with LAI overlap. Patients were compared based on LAI administration time to CIVI initiation: Early (<12 hours) versus Late (≥12 hours). The DKA resolution is defined as blood glucose < 200 mg/dL and 2 of the following: anion gap < 12 mEq/L, pH > 7.35, or serum carbon dioxide >15 mEq/L. Outcomes included time to DKA resolution, length of stay (LOS), CIVI duration, and adverse events. A total of 27 patients were included in each group. Baseline characteristics were similar between both groups. There was no difference in time to DKA resolution, Early = 17.6 (13.9-26.8) hours versus Late = 19.2 (17.1-32.1) hours, P = 0.16. The Early group had shorter CIVI duration (Early = 19.5 ± 10.3 hours vs Late = 25.6 ± 8.4 hours, P = 0.02) and received less intravenous (IV) fluids in the first 36 hours (Early = 4.04 ± 2.12 L vs Late = 5.85 ± 2.24 L, P = 0.004). No differences were identified with adverse events, including hypoglycemia, or LOS. Administration of SQ LAI < 12 hours did not decrease time to DKA resolution or LOS. Patients in the Early group had received a lower dose of LAI, shorter duration of CIVI infusion, and required less IV fluids within 36 hours of admission. This study supports the need for further research to determine the potential benefits of administering SQ insulin early in managing DKA.

Efficacy of subcutaneous insulin lispro versus continuous intravenous regular insulin for the treatment of patients with diabetic ketoacidosis

Effectiveness and Safety of Early Insulin Glargine U100 and Glargine U300 Administration in the Management of Diabetic Ketoacidosis in Adults With Type 1 Diabetes Mellitus: A Randomized Clinical Trial.

Diabetic ketoacidosis (DKA) frequently requires emergency admission. The anion gap approach is conventionally used for the diagnosis and documenting the resolution of acidosis during treatment. However, it fails to detect hyperchloremic acidosis during the resolution and may result in the prolongation of treatment. To determine the role of the Stewart approach of acid-base disorder during DKA management for the prediction of an earlier resolution. A prospective comparative study was conducted between January 2017 and December 2017 at a single academic hospital in north India. Patients aged above 12 years with a diagnosis of DKA were randomly divided into two groups—the conventional group and the Stewart group, according to the approach used for DKA resolution. The primary outcome was the time duration required for resolution. The secondary outcomes were the therapeutic requirement of intravenous fluid, insulin, and potassium, Acute Physiology and Chronic Health Evaluation II (APACHE II) score at the time of resolution, and hospital stay. Forty-four DKA patients were equally distributed in the two groups with comparable baseline parameters. The Stewart group had early resolution of DKA (mean, 32.4±17.5 h versus 41.7±19.6 h; p value <0.001) at similar APACHE II scores. The duration of hospital stay was reduced but was not statistically significant (mean, 5.6±3.2 days versus 7.0±3.8 days; p value 0.16). The therapeutic requirement of fluid, insulin, and potassium was similar in groups. The Stewart approach may be a better alternative to the conventional anion gap approach for guiding the resolution of DKA.

We previously implemented the subcutaneous (SQ) insulin in diabetic ketoacidosis (DKA) (SQuID) protocol, demonstrating safe, effective treatment of low to moderate (LTM) severity DKA in a non-intensive care unit setting. SQuID replaces intravenous (IV) insulin with SQ injections and reduces glucose checks from hourly to every 2 hours. We are not aware of any data on patient satisfaction with treatment in DKA. Our objective was to compare satisfaction in patients treated with IV insulin to that in patients treated with the SQ protocol. We conducted a cross-sectional study in an urban academic hospital (March 2023 to March 2024) of emergency department patients treated for LTM DKA with SQ or IV insulin. Patients were contacted by phone in the hospital after the resolution of DKA. We used the validated 21-item Diabetic Treatment Satisfaction Questionnaire-Inpatient tool (DTSQ-IP) using 7-tier Likert-style options (0= negative; 6= positive) to assess patient satisfaction with treatment. We computed the DTSQ-IP composite treatment satisfaction score (using 15 of the 21 items), assessing differences between groups. Of the 60 patients contacted, 52 (87%) completed the questionnaire. Median DTSQ-IP satisfaction scores for SQuID and IV insulin patients were 86.0 (IQR, 79.0, 88.0) and 81.0 (IQR, 77.0, 88.0), respectively. We found no difference in satisfaction between groups (difference 5.0; 95% CI,-3.0, 10.0). In this single-center study, patient satisfaction with DKA care was high, with no differences observed between patients treated with SQ vs IV insulin protocols. This is the first study we are aware of on patient satisfaction with treatment in DKA or treatment with SQ insulin. Though the sample size is small, these findings suggest that patient satisfaction should not represent a barrier to the implementation of SQ protocols for LTM severity DKA.

Managing Diabetic Ketoacidosis in Children

BackgroundThe aim of the study was to identify the intrinsic patient characteristics and extrinsic environmental factors predicting prescription and use and, more specifically, early initiation (up to 5 years of disease duration) of insulin for type 2 diabetes in France. A secondary objective was to evaluate the impact of insulin therapy on mental and physical quality of life and patient adherence.MethodsThe data used in this study were derived from the 2008, 2010, and 2011 France National Health and Wellness Survey. This survey is an annual, cross-sectional, self-administered, Internet-based questionnaire among a nationwide representative sample of adults (aged 18 years or older). Of the total of 45,958 persons recruited in France, 1,933 respondents (deduped) were identified as diagnosed with type 2 diabetes. All unique respondents from the three waves, currently using insulin or oral bitherapy or tritherapy at the time of assessment, were included in this analysis.ResultsEarly (versus late) initiation of insulin therapy was 9.9 times more likely to be prescribed by an endocrinologist or diabetologist than by a primary care physician (P < 0.0001). Younger age at diagnosis and current smoking habits were significant predictors of early (versus late) insulin initiation (odds ratio [OR] 1.031, 95% confidence interval [CI] 1.005–1.059, P = 0.0196, and OR 2.537, 95% CI 1.165–5.524, P = 0.0191, respectively). Patients with a yearly income ≥€50,000 were less likely to be put on insulin early (P = 0.0399). A link between insulin prescription and complications was shown only in univariate analysis. Mental quality of life was lower in patients on early (versus late) insulin, but only in patients with diabetes-related complications. Insulin users (versus oral bitherapy or tritherapy users) had 3.0 times greater odds of being adherent than uncontrolled oral bitherapy or tritherapy users (OR 2.983, 95% CI 1.37–6.495, P = 0.0059).ConclusionThis study confirms the role of specialists in early initiation of insulin, and the data presented herein reflect the fact that early initiation is more frequent in younger patients, patients with diabetes-related complications, and current smokers, and less frequent in patients with a higher income. Moreover, we observed that being treated with insulin was not associated with deterioration in quality of life, and insulin-treated patients were more often adherent than uncontrolled oral bitherapy or tritherapy users. These data suggest that doctors’ concerns about patient adherence and detrimental effects on quality of life should not be a barrier to their decision regarding early initiation of insulin therapy. Due to the nature of this cross-sectional survey (eg, inability to assess treatment flow), further research is needed to confirm its findings.

Continuous glucose monitoring (CGM) devices are increasingly used in critical and non-critical care hospital units. The efficacy of CGM in assessing glucose control in adults with diabetic ketoacidosis (DKA) is unknown. This single-center pilot study compared glycemic control by real-time CGM (Dexcom G6), capillary point-of-care (POC), and basic metabolic panel (BMP) during intravenous (IV) insulin treatment and after the resolution of DKA. We compared the mean absolute relative difference (MARD), median absolute relative difference (ARD) glucose values, and Diabetes Technology Society (DTS) Error Grid analyses. We recruited 52 patients (49 ± 19 years, admission glucose: 503 ± 239.4 mg/dL) with type 1 diabetes (n = 24) and type 2 diabetes (n = 28). Compared with POC testing, the MARD was 17.4% ± 13.2%, and the median ARD was 14.2% (interquartile range [IQR]: 6.4, 28) during the initial IV insulin period and 19.8% ± 18.7% and 14.3% (7, 26.2) after DKA resolution. The DTS Error Grid analysis showed that 100% of values during the IV insulin treatment and 95% after the DKA resolution were in zones A+B. Compared with BMP glucose values, the MARD and median ARD were 18.5% ± 19.1% and 12.2% (5.4, 23.8) during the IV insulin treatment and 22.5% ± 24.7% and 15.1% (6.6, 27.6) after DKA resolution. This is the first report on the use of real-time CGM in adults with DKA. Our study indicates that CGM technology is a reliable tool for hospital use during acute insulin treatment and after the resolution of DKA. Future multicentre randomized studies are needed to determine the benefits of real-time CGM in facilitating diabetes care in hospitalized patients with hyperglycemic crises.

To determine the effectiveness and safety of early combination of insulin glargine with intravenous (IV) insulin infusion compared with IV insulin infusion alone in the management of diabetic ketoacidosis (DKA). This was a single-centre, open-label, randomized controlled trial of adults aged 18 years or older diagnosed with DKA. The 'early glargine' group was given subcutaneous insulin glargine 0.3 units/kg within the first 3 hours of DKA diagnosis, in addition to the standard IV insulin infusion. The control group received standard IV insulin treatment only. The primary outcome was the time to DKA resolution. The other outcomes included rebound hyperglycaemia, mortality, hypoglycaemia and hypokalaemia, as well as the length of hospital stay (LOS). A total of 60 patients (30 patients per group) were enrolled. Most patients (76.7%) had type 2 diabetes. Both groups were similar in baseline characteristics, except for higher serum beta-hydroxybutyrate and lower pH levels in the early glargine group. The mean ± standard deviation time to DKA resolution in the early glargine group was significantly faster than the control group (9.89 ± 3.81 vs. 12.73 ± 5.37 hours; P=.022). The median (interquartile range) LOS was significantly shorter in the early glargine group than in the control group (4.75 [3.53-8.96] vs. 15.25 [5.71-26.38] days; P=.024). The incidence of rebound hyperglycaemia, all-cause mortality, hypoglycaemia and hypokalaemia was similar between the groups. Early combination of insulin glargine with IV insulin infusion led to a faster DKA resolution and a shorter LOS, without increasing hypoglycaemia and hypokalaemia.

AimsTo 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 MethodsA 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.ResultsEight 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.ConclusionsEarly 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.

Management of acute hyperglycemic emergencies: focus on diabetic ketoacidosis.

Background: Diabetic ketoacidosis (DKA) is an acute metabolic healthcare crisis in patients with diabetes mellitus. The current study aimed to compare the effectiveness of rapid-acting insulin analog administered subcutaneously with regular insulin infused intravenously among the DKA patients. Methodology: In this prospective open labelled study, 100 consecutive DKA patients were randomly assigned to two groups. Group 1 patients were admitted to the intensive care unit (ICU) and treated with intravenous regular insulin infusion. Group 2 patients were managed in the emergency medical ward with subcutaneous rapid-acting insulin. Response to the therapy was assessed by the follow-up investigations of the biochemical parameters, including blood glucose concentration, serum ketones, pH, serum electrolytes including bicarbonates, sodium and potassium concentration until the resolution of DKA. Furthermore, the overall duration of therapy (blood glucose level &lt; 250 mg/dl), time and amount of insulin administered until the resolution of DKA, were also assessed. Results: The baseline clinical and biochemical parameters were similar between the two treatment groups except for blood glucose and sodium concentration. The mean random blood sugar (RBS), acid-base parameters and concentration of ketone bodies were significantly improved from admission until the resolution of DKA. There was no significant difference in the duration of therapy (p=0.07). While the time and amount of insulin therapy required until resolution of DKA were significantly reduced among the patients treated subcutaneously with rapid-acting insulin, i.e. 16.36 ± 6.92 hrs and 59.28 ± 30.05 units (p&lt;0.05). Conclusion: The patients with less complicated DKA can be managed with rapid-acting insulin analog in the medical wards obviating the need for admission to the ICU. With relatively better outcomes, it is an effective alternative to regular intravenous insulin infusion for DKA resolution.

Introduction: Diabetic ketoacidosis (DKA) remains a significant complication of diabetes in the world and is associated with high rates of hospital admissions. In mild, uncomplicated cases of DKA a subcutaneous regimen of newer rapid-acting insulin analogues has been proposed as a safe and effective alternative to intravenous regular insulin in prospective, randomized trials. Our primary objective is to compare the efficacy and safety of intermittent subcutaneous (SC) rapid insulin administration with continuous intravenous (IV) regular insulin infusion in the treatment of mild to moderate DKA. Methodology: A retrospective chart review of all adult Filipino patients admitted for mild to moderate DKA at UST Hospital private and clinical divisions from 2012 – 2015 was done. Chart cases were divided into two groups, namely: group one who received IV infusion of regular insulin and group two who received SC rapid insulin analog as treatment. The clinical and biochemical characteristics of the patients on admission were obtained. Efficacy and safety of both treatment regimens were compared as to the duration of time and amount of insulin administered from admission until resolution of DKA was achieved, occurrence of hypoglycemia and hypokalemia, mortality and length of hospitalization. Results: Twenty-one chart cases were included, twelve in the continuous IV insulin infusion group and nine in the intermittent SC rapid insulin group. The baseline characteristics of patients were almost similar. There was no significant difference between the treatment groups in the duration of time and amount of insulin administered to achieve DKA resolution, occurrence of hypoglycemia, and death. Hypokalemia occurred more frequently and hospital stay was longer in the IV insulin group. Conclusion: Intermittent subcutaneous rapid insulin regimen is an effective, safe, and potentially cost-effective alternative to continuous intravenous insulin infusion for treatment of mild to moderate cases of DKA. Keywords: Diabetic ketoacidosis, rapid insulin analogue, regular insulin infusion, efficacy and safety