Delays in anti-hyperglycaemic therapy initiation and intensification are associated with cardiovascular events, hospitalizations for heart failure and all-cause mortality

Aims The aims of this study were to assess the impact of delays in treatment intensification (TI) on cardiovascular events, heart failure, and all-cause mortality at typical stages of anti-hyperglycaemic therapy. Materials and Methods Using electronic health record data, we created three TI cohorts of diabetes patients who: 1) initiated metformin (MET) as their first anti-hyperglycaemic therapy; 2) added a sulfonylurea (SU) to MET; and 3) initiated insulin (INS) while using MET or SU, alone or in combination. Primary exposure variables were haemoglobin A1C value preceding cohort therapy (pre-TI A1C) and time to intensification, that is, the time between pre-TI A1C >7% and cohort index date. Cox regression models were used to analyse the associated risk of cardiovascular events, hospitalizations for heart failure and all-cause mortality. Results In the MET cohort, each additional percentage point of pre-TI A1C was associated with a 10% increased risk of a CV event (HR, 1.10; 95% CI, 1.03-1.07; P = 0.004), a 7% increased risk of HF hospitalization (HR, 1.07; 95% CI, 1.01-1.14; P = 0.034) and a 7% increased risk of all-cause mortality (HR, 1.07; 95% CI, 1.01-1.14; P = 0.032). Pre-TI A1C was associated with a 9% increased risk of a CV event in the INS cohort (HR,1.09; 95% CI, 1.04-1.13; P < 0.001). Each month of delay in TI was significantly associated with a 6% increased risk of hospitalization for HF (HR, 1.06; 95% CI, 1.00-1.13; P = 0.040) and all-cause mortality (HR, 1.06; 95% CI, 1.00-1.13; P = 0.050) in the MET cohort. Conclusions Delays in TI were associated with poor outcomes over a mean follow-up period of nearly five years. Earlier initiation and more rapid intensification of pharmacotherapy could reduce the risk of poor outcomes.