Aims: To investigate whether a rapid reduction in HbA1c is more effective for reducing diabetes-related complications and mortality than a gradual approach in patients with severe hyperglycemia.

Methods: This retrospective cohort study included 577 patients with type 2 diabetes and an initial HbA1c level ≥ 9.0%, recruited from the Diabetes Shared Care Program at the Taipei Veterans General Hospital from January 2004 to December 2015 and followed up until December 2019. Participants were divided into two groups based on the rate of HbA1c reduction: rapid (HbA1c level < 9.4% by month 3) and slow (HbA1c level ≥ 9.4% by month 3). Primary outcomes were nephropathy, retinopathy, and all-cause mortality. Data were analyzed using Cox proportional hazards models, adjusted for potential confounders.

Results: The rapid-reduction group exhibited significantly lower mean HbA1c levels over five years and risk of all-cause mortality (Hazard Ratio [HR]: 1.371; 95% CI: 1.026-1.833; p = 0.033) than the slow-reduction group. In the subgroup without substantial baseline diabetes-related complications, the rapid-reduction group had lower risks of urine albumin/creatinine ratio ≥ 300 mg/g (HR: 1.441; 95% CI: 1.011-2.055; p = 0.043), any retinopathy (HR: 1.497; 95% CI: 1.079-2.076; p = 0.016), and all-cause mortality (HR: 1.456; 95% CI: 1.034-2.050; p = 0.031) than the slow-reduction group.

Conclusion: Rapid reduction of HbA1c levels significantly reduces risk of all-cause mortality in patients with severe hyperglycemia. It also reduces risk of nephropathy and retinopathy in patients without substantial diabetes-related complications at baseline.