Delays in Antihyperglycemic Treatment Intensification and Risk of Diabetes Complications

Longer delays in anti-hyperglycemic treatment intensification (TI) are associated with poorer glycemic control, but whether these delays increase the risk of poor outcomes is unclear. We combined 2005-2016 data from the Northwest and Mid-Atlantic regions of Kaiser Permanente to identify 3 cohorts of patients who intensified therapy by: 1) initiating metformin (MET) as their 1st diabetes drug (n=18,762); 2) adding a sulfonylurea (SU) to existing MET (n=10,076); 3) initiating insulin after MET and/or SU therapy (n=9,778). We used the TI date to calculate time between A1C ≥7% and TI, pre-TI A1C, and achievement of A1C >7% within 1 year. From the ∼1-year post-TI A1C, we followed patients through December 2016 until they experienced an MI, stroke, or other cardiovascular (CV) event, a heart failure (HF) hospitalization or all-cause mortality, censoring follow-up when the cohort therapy changed. Multivariable cox regression controlled for CV risk factors including age, sex, race/ethnicity, smoking, blood pressure, statin and ACE/ARB use, and prior history of CV or HF. After adjustment for CV risk factors, Pre-TI A1C and time from A1C ≥7% to TI date was significantly associated with the outcomes (Table). Delays in treatment intensification increase CV, HF and mortality risk at all stages of diabetes therapy; intensifying therapy at the first sign of deteriorating glycemic control may be critically important.