HbA1c-based personalization of glucose management in critical illness: a target trial emulation.

OBJECTIVE: To evaluate the effect of HbA1c-guided glycaemic control on 30-day intensive care unit mortality in intensive care unit patients. DESIGN: Target trial emulation using the parametric g-formula. Setting: A single tertiary academic hospital intensive care unit in Melbourne, Australia. Patients: All adults admitted between January 2019 and December 2023 with an admission HbA1c measurement and complete intensive care unit admission/discharge data. Interventions: Three glucose control strategies were compared: natural course (usual care), NICE-SUGAR target (8 - 10mmol/L), and personalised HbA1c-guided target (usual glycaemia ± 0.8mmol/L). RESULTS: Among 3,541 patients (64% male, median age 68 years), mortality was 6.46% (95%CI 4.16% - 8.83%) under the natural course, 6.52% (95%CI 4.40% - 8.82%) with NICE-SUGAR, and 6.56% (95%CI 4.40% - 8.85%) with HbA1c-guided targets. Absolute risk differences versus usual care was 0.10% (95%CI -0.26% - 0.93) for HbA1c-guided strategy. Subgroup analyses by diabetes status, admission type, illness severity, and septic shock showed no survival benefit. CONCLUSION: In this large single-centre target trial emulation, personalising glycaemic targets based on admission HbA1c did not improve 30-day intensive care unit mortality compared with either usual care or NICE-SUGAR targets. These findings suggest that HbA1c-guided glucose control is unlikely to confer meaningful survival benefit under current implementation approaches.