A Pragmatic Cluster-Randomized Trial of Insulin Therapy for Dexamethasone-Induced Hyperglycemia Amongst Diabetes Patients with COVID-19

Background: Glucocorticoid-induced hyperglycemia is common amongst hospitalized patients. Isophane insulin has been proposed as part of the optimal insulin regimen for managing this, but there are few randomized controlled trials to support this. Our aim was to determine if the addition of a morning dose of isophane insulin would improve glycemic control amongst patients with COVID-19 who had dexamethasone-induced hyperglycemia (DIH) in hospital. Methods: Patients with diabetes admitted to hospital with COVID-19 respiratory infection and treated with dexamethasone were cluster-randomized by ward to receive either basal bolus insulin (BBI) or isophane-augmented BBI (IaBBI) in equipotent doses. Insulin commencement and titration were guided by standardized protocols. The primary outcome was overall finger-prick blood glucose (BG) levels, with predefined secondary outcomes of BGs on day 3 and the final day of admission. Results: A total of 40 patients were included, 25 in the IaBBI group and 15 in the BBI only group, for a duration of 5.4 ± 2.2 days. Both recruitment and the trial were terminated early because of a rapid decline in COVID-19 admissions. There were no differences in overall mean BG levels (IaBBI 11.9 ± 2.5 mmol/L vs. BBI 12.6 ± 2.4 mmol/L, p = 0.193) between the groups. Mean day 3 BGs were lower in the IaBBI group than in the BBI group (11.1 ± 3.5 mmol/L vs. 12.7 ± 3.5 mmol/L, p = 0.029) and on the final day (9.6 ± 2.8 mmol/L vs. 10.7 ± 2.5 mmol/L, respectively, p = 0.011). Conclusions: The restricted sample size in this study limits any conclusions that can be made regarding the effectiveness of the addition of isophane insulin to a BBI insulin regimen for diabetes patients with COVID-19 infection and DIH. However, some improvements in glycemic control were observed, suggesting that this is a glucose management strategy that warrants further evaluation.