Effect of Early vs Delayed or No Insulin Therapy for Moderate Hyperglycemia in Patients in the ICU: A Target Trial...

Hyperglycemia is common in patients in the ICU and associated with increased mortality. Despite several randomized clinical trials of glucose management in critical illness, the effects of insulin treatment and its timing in patients with moderate hyperglycemia remain uncertain.

In acutely admitted patients in the ICU with moderate hyperglycemia, does insulin treatment improve clinical outcomes, and does timing of insulin initiation matter?

We performed a multicenter target trial emulation using targeted minimum loss-based estimation. Patients from 4 ICUs at Karolinska University Hospitals (Solna, Huddinge) from 2010 to 2021 were included. The effect of early insulin treatment compared with delayed or no insulin treatment on 30-day all-cause mortality was assessed in acutely admitted adult patients in the ICU with moderate hyperglycemia (10-13.9 mM).

The study included 5,755 patients with moderate hyperglycemia; 3,149 (54.7%) received early insulin therapy (intervention group) and 2,606 (45.3%) received delayed or no insulin therapy (control group). The adjusted 30-day mortality was 22.1% (95% CI, 21.1-23.1) for patients receiving insulin within 6 hours and 24.4% (95% CI, 23.5-25.4) for patients with later or no insulin treatment, corresponding to an absolute risk reduction of 2.3% (95% CI, 1.1-3.6). Absolute risk was reduced by 7.7 percentage points (95% CI, 6.5-8.9) when insulin was initiated within 1 hour of the first episode of moderate hyperglycemia and by 6.6 percentage points (95% CI, 5.4-7.8) with initiation within 2 hours. This effect was modified in several subgroups.

In this target trial emulation, early insulin treatment of moderate hyperglycemia showed reduced mortality in acutely admitted adult patients in the ICU, particularly when insulin was initiated within 2 hours following hyperglycemia. These findings support further investigation into the timing of insulin initiation.