Cardiovascular Outcomes Trials Update: Insights from the DEVOTE Trial.

Abstract

The DEVOTE study compared the cardiovascular safety of two basal insulins, degludec, and glargine U100 in patients with type 2 diabetes (T2D) at high risk for cardiovascular disease (CVD). In this review, we summarize the results of DEVOTE and provide a clinical perspective. DEVOTE was a phase 3b, multicenter, international, treat-to-target, double-blind, event-driven trial. Patients with T2D > 50years of age with prior CVD or > 60years of age with CVD risk factors were randomly assigned to receive either degludec (n= 3818) or insulin glargine U100 (n= 3819) and were followed until at least 633 positively adjudicated major adverse cardiovascular events (MACE; cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) accrued. At baseline, the mean age of the subjects was 65.0years, the mean duration of diabetes was 16.4years, and the mean HbA1c was 8.4 ± 1.7%. After a median follow-up of 2years, HbA1c had decreased to 7.5 ± 1.2% in each group. Degludec was non-inferior to insulin glargine U100 with respect to the primary MACE outcome (hazard ratio 0.91; 95% CI 0.78-1.06). Significantly, lower rates of severe hypoglycemia and nocturnal severe hypoglycemia were observed with degludec compared to glargine U100 (rate ratios of 0.60; 95% CI 0.48-0.76 and 0.47; 95% CI 0.31 to 0.73, respectively). DEVOTE demonstrated that the cardiovascular safety of degludec was comparable to that of insulin glargine U100 in patients with T2D at high risk for CVD. Additionally, degludec was superior to insulin glargine U100 with respect to the risk for severe hypoglycemia. These results suggest that degludec might be preferred in patients at risk for severe hypoglycemia, including the elderly, those with CVD and/or those with chronic kidney disease.