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Introduction Prednisolone is widely prescribed to hospitalized patients for a range of conditions. Up to 40% of hospitalized patients treated with prednisolone will experience hyperglycemia. Current guidelines recommend management of acute hyperglycemia in hospitalized patients with subcutaneous basal-bolus insulin (BBI), but the optimum treatment strategy has not been defined. We aimed to assess the performance of an individualized subcutaneous BBI regimen for management of prednisolone-associated hyperglycemia in hospitalized patients.Research design and methods This cross-sectional study included 23 adult inpatients prescribed subcutaneous BBI based on total daily insulin requirements estimated from a 24-hour intravenous insulin infusion and 24 historical controls who were prescribed a standard, institutional weight-based subcutaneous BBI to treat prednisolone-associated hyperglycemia. The primary endpoint was the mean 24-hour point-of-care (POC) glucose concentration on day 1. Exploratory end points included proportion of glucose measurements within target glucose range, SD of glucose, and stress hyperglycemia ratio (SHR).Results There was no significant difference in mean POC glucose on day 1 between participants prescribed an individualized insulin regimen and patients receiving a standard body weight-based BBI regimen (10.7±3.4 vs 11.9±3.2 mmol/L, p=0.07). Proportion of glucose measurements within the target glucose range was higher (52.0±4.8 vs 37.0±4.5%, p=0.0007) and SD for glucose lower (3.1±1.5 vs 4.0±1.6, p=0.04) on day 1 of individualized BBI insulin. Over 2 days, there was an increase in glucose SD in both groups, but no significant difference in mean glucose and SHR between groups.Conclusions Individualizing a subcutaneous BBI regimen for management of prednisolone-associated hyperglycemia was associated with a modest reduction in mean POC glucose, an increased proportion of blood glucose measurements within the target range, and reduced short-term glycemic variability.Trial registration number ACTRN12618001211257.