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

Abstract

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.

Effects of naringenin on vascular changes in prolonged hyperglycaemia in fructose-STZ diabetic rat model

“…Therefore, longer exposure of the cells to the hyperglycaemic condition caused increased in oxidative stress thus more difficult in treating the hyperglycaemic conditions (31). Prolonged hyperglycaemia is also known to affect the prognosis and outcome of patients as delay in the intensification of treatment might increase risk in developing cardiac event that could lead to fatality (32). In this study, metformin treatment also showed no significant reduction in blood glucose.…”

Clinical efficacy and cost‐effectiveness of metformin in different patient populations: A narrative review of real‐world evidence

“…The protective effect of metformin seems to be influenced by the rapidity of therapy initiation, the persistence with treatment, and distinct patient characteristics. An analysis of electronic health records of the Kaiser Permanente Northwest and Mid‐Atlantic States regions demonstrated that a delayed initiation of metformin therapy in drug‐naïve patients was associated with a significantly increased risk of hospitalization for heart failure and all‐cause mortality 40 . A recent Italian case–control study evaluated the protective effect of oral hypoglycaemic agents in a large cohort of elderly T2D subjects, 67% of whom were on metformin treatment 41 .…”

“…An analysis of electronic health records of the Kaiser Permanente Northwest and Mid-Atlantic States regions demonstrated that a delayed initiation of metformin therapy in drug-naïve patients was associated with a significantly increased risk of hospitalization for heart failure and all-cause mortality. 40 A recent Italian case-control study evaluated the protective effect of oral hypoglycaemic agents in a large cohort of elderly T2D subjects, 67% of whom were on metformin treatment. 41 The study concluded that, with the exception of very elderly patients (aged >85 years), increased adherence to metformin therapy was associated with reduced risk of mortality.…”

Glycaemic profiles of diverse patients with type 2 diabetes using basal insulin: MOBILE study baseline data

“…When facing elevated HbA1c levels, patients are often daunted by factors such as their own or their provider's reluctance to change (‘therapeutic inertia’), regimen complexity or cost. There are often long 2 and detrimental 3 delays in initiating or intensifying insulin as a result.…”