K. Vidyasagar, B. Chandrasekar, M. Chhabra, A. Bhansali and D. Bansal (2020). Efficacy and Safety of Commonly Used Insulin Analogues in the Treatment of Diabetic Ketoacidosis: A Bayesian Indirect Treatment Comparison. Clinical therapeutics, 42(8), e115-e139. https://doi.org/10.1016/j.clinthera.2020.06.017

PubMed 32798057

[Abstract]
PURPOSE: Insulin analogues (IAs) are the mainstay for the management of diabetic ketoacidosis (DKA). However, the relative efficacy of newer IAs is uncertain. The aim of this study was to compare the relative efficacy and safety of IAs for the management of DKA using an indirect treatment comparison (ITC).

METHODS: PubMed, EMBASE, Scopus, the Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) comparing short-, rapid-, and long-acting IAs in patients with DKA. The primary outcomes of interest were time taken to normalize DKA and time taken to normalize blood glucose levels. The secondary outcomes of interest were the amount of insulin needed to normalize DKA, the length of hospital stay, and the number of hypoglycemic events in the intervention and comparator groups. Bayesian ITC was performed by using the gemtc package in the R program. Continuous outcomes are reported as mean difference (MD), and binary outcomes are reported as odds ratios (ORs), with 95% credible intervals (CrIs). The Cochrane risk of bias tool was used to assess the risk of bias in the included RCTs.

FINDINGS: Ten RCTs randomizing 435 participants to treatment were included in this ITC. A total of 5 interventions (lispro, glargine with regular insulin [RI], glulisine, aspart, and regular insulin) were compared for both safety and efficacy outcomes in DKA. Glargine co-administered with regular insulin showed superiority for clinical outcomes compared with regular insulin: consuming less time (MD, -3.1 h; 95% CrI, -7.9 to 1.8), amount of insulin required (MD, -32 U; 95% CrI, 83.0 to 18.0), and the length of hospitalization (MD, -0.82 day; 95% CrI, -2.7 to 1.0) to normalize DKA. However, these results were not statistically significant. Insulin aspart had fewer reports of hypoglycemic events (OR, 1.7; 95% CrI, 0.34 to 9.3) than regular insulin.

IMPLICATIONS: Newer IAs were found to be equally effective and safe as regular insulin in the treatment of DKA. Thus, administering these IAs can be considered a safe and cost-effective alternative for DKA management in non-ICU settings. Cost-effective analysis of the newer IAs is needed because these agents are expensive compared with regular insulin.