Subcutaneous fast-acting insulin analogues, alone or in combination with long-acting insulin, versus intravenous regular insulin infusion in patients with diabetic ketoacidosis: protocol for an updated systematic review and meta-analysis of randomised trials

Abstract

IntroductionDiabetic ketoacidosis (DKA) is traditionally managed using intravenous regular insulin infusion (RII) in intensive care unit (ICU)/high dependency unit (HDU). Subcutaneous fast-acting insulin analogues (FAIAs) may help to manage DKA outside ICU/HDU. Furthermore, combining subcutaneous long-acting insulin (LAI) with subcutaneous FAIAs may accelerate ketoacidosis resolution. The latest (2016) Cochrane review was inconclusive regarding subcutaneous FAIAs versus intravenous RII in DKA. It was limited by small sample sizes, unclear risk of bias (RoB) in primary trials and did not examine subcutaneous FAIAs with subcutaneous LAI versus intravenous RII in DKA. We report the protocol for an updated meta-analysis on the safety and benefits of subcutaneous FAIAs with/without subcutaneous LAI versus intravenous RII in DKA.Methods and analysisWe will search Medline, Embase, CINAHL and Cochrane Library, from inception until December 2022, without language restrictions, for randomised trials on subcutaneous FAIAs with/without subcutaneous LAI versus intravenous RII in DKA. We also search ClinicalTrials.gov, ClinicalTrialsRegister.eu and reference lists of included trials. Primary outcomes include all-cause in-hospital mortality, time to DKA resolution, in-hospital DKA recurrence and hospital readmission for DKA post-discharge. Secondary outcomes include resource utilisation and patient satisfaction. Safety outcomes include important complications of DKA and insulin. Reviewers will extract data, assess overall RoB and quality of evidence using Grading of Recommendations, Assessment, Development and Evaluation. We will assess statistical heterogeneity by visually inspecting forest plots and the I2statistic. We will synthesise data using the random-effects model. Predefined subgroup analyses are: mild versus moderate versus severe DKA; age <20 vs ≥20 years; pregnant versus non-pregnant; infective versus non-infective DKA precipitating cause; subcutaneous FAIAs alone versus subcutaneous FAIAs and subcutaneous LAI; and high versus low overall RoB. We will also perform trial sequential analysis for primary outcomes.Ethics and disseminationEthics board approval is not required. Results will be disseminated through publication in a peer-reviewed journal.PROSPERO registration numberCRD42022369518.

The effects of subcutaneous insulin aspart in treatment of non-severe diabetic ketoacidosis

“…Correction of electrolyte disturbances, identi cation and treatment of predisposing conditions, careful clinical evaluation and monitoring of vital signs and biochemical parameters are critical [6][7][8][9][10]. Continuous intravenous (IV) infusion of low-dose regular insulin in an intensive care unit (ICU) or high dependency unit where appropriate intensive nursing care and access to laboratory test results are available is the standard protocol of insulin therapy in the patient with DKA [11,12]. Compared to subcutaneous injections, infusion of IV insulin and ICU admission requires more drugs and equipment and more care provided by experienced nursing staff which creates a signi cant economic burden.…”