Insulin Glulisine Versus Regular Human Insulin for Prednisolone-Associated Hyperglycemia Assessed by Continuous Glucose Monitoring: An Open-Label Crossover Study

Background: Steroid (glucocorticoid)-induced hyperglycemia is common in hospitalized patients treated with prednisolone and often requires prandial insulin. Evidence is limited regarding whether rapid-acting insulin analogs provide different glycemic profiles compared with regular human insulin under protocol-based titration. Methods: We conducted a single-center, non-randomized, open-label, crossover study in hospitalized adults with type 2 diabetes or steroid-induced diabetes who were receiving morning oral prednisolone (≥5 mg/day) and required insulin therapy. After an insulin dose-adjustment period (with non-insulin agents withheld throughout the dose-adjustment and study periods), participants received insulin glulisine and regular human insulin on consecutive study days without a washout interval, switching unit-for-unit at identical pre-meal doses. Glucose profiles were assessed using continuous glucose monitoring (CGM). Primary endpoints were total glucose area under the curve (AUC) over 0-24 hours and time-segment AUCs (0-8, 8-12, 12-18, and 18-24 hours). Results: Thirteen of 26 eligible patients provided informed consent; six were excluded because >25% of expected CGM readings were missing, all due to device-related recording issues, leaving seven patients for analysis. The total AUC did not differ between insulin glulisine and regular human insulin (118.02 ± 30.95 vs 117.41 ± 30.20 ×10^2 mmol/L·min; P = 0.925), and no significant differences were observed in time-segment AUCs. Mean glucose, maximum glucose, minimum glucose, mean amplitude of glycemic excursions, and time-in-range metrics were similar. Coefficient of variation was lower with insulin glulisine (28.81 ± 9.05% vs 34.55 ± 8.96%; P = 0.034). In an exploratory post hoc analysis within a 30-minute time window around 16:00, AUC, mean glucose, and maximum glucose were lower with regular human insulin than with insulin glulisine (P < 0.05). Conclusions: Under protocol-based titration during prednisolone treatment, insulin glulisine and regular human insulin produced comparable overall 24-hour glucose exposure. Findings on glycemic variability and post hoc time window analyses should be interpreted as exploratory and warrant confirmation in larger studies.