Hyperglycemia and insulin use in patients with COVID-19 and severe hypoxemia allocated to 12 mg vs. 6 mg of dexamethasone: a secondary analysis of the COVID STEROID 2 randomized trial.

Background: While dexamethasone has been shown to improve survival in COVID-19, its dose-response relationship with plasma glucose (PG) levels and insulin requirements is poorly understood. This study investigated the impact of 12 mg (higher dose) versus 6 mg (standard dose) of dexamethasone on hyper- or hypoglycemic events and the use of insulin.

Methods: A secondary analysis of a subpopulation of the COVID STEROID 2 trial. Glycemic outcomes were assessed by time-to-event analysis of a hyperglycemic (two PG measurements ≥ 11.1 mmol/L), severe hyperglycemic (PG > 20 mmol/L), hypoglycemic (< 3.8 mmol/L) event or use of insulin, adjusted for age, diabetes status, hospital site, and mechanical ventilation. PG levels were compared before and after treatment allocation with linear mixed models to estimate changes in average PG levels over time.

Results: Of 321 participants, 170 were allocated to the higher dose and 151 to the standard dose of dexamethasone. Time to a hyperglycemic event did not differ between groups, whereas severe hyperglycemic events were more frequent in the higher dose group (36%) than in the standard dose group (31%) with an adjusted subdistributional hazard ratio of 1.76 (95% CI [1.22-2.54], p = 0.003). Insulin use and hypoglycemic events did not differ between groups. The higher vs. standard dose group had an average PG increase of 0.5 mmol/L (95% CI [- 0.2 to 1.4], p = 0.149).

Conclusion: Higher vs. standard doses of dexamethasone were associated with a higher incidence of severe hyperglycemia in patients with COVID-19 and severe hypoxemia, but the average increase in PG was similar between groups.