New, long-acting insulin is safe and lowers the rate of severe and nocturnal hypoglycemia events
The primary results from DEVOTE were presented at the American Diabetes Association's 77th Scientific Sessions and published simultaneously in NEJM. DEVOTE is the first randomized, double-blind, treat-to-target, event-driven trial comparing two basal insulins, insulin degludec injection 100 U/mL and insulin glargine U100, in adults with type 2 diabetes (T2DM) at high risk of cardiovascular (CV) disease. Insulin degludec is a once-daily long-acting insulin indicated to improve glycemic control in patients 1 year of age and older with diabetes.
The trial, involving 7,637 people with T2DM followed for approximately two years, demonstrated that insulin degludec met the primary endpoint of non-inferiority compared with insulin glargine U100 for major adverse CV events (MACE) with a HR of 0.91 (95%CI: 0.78-1.06, p=0.209). Additionally, the findings for each component of MACE were consistent with the overall endpoint, including first occurrence of CV death (HR=0.96, 95%CI: 0.76-1.21, p=0.714), non-fatal myocardial infarction (MI) (HR=0.85, 95%CI: 0.68-1.06, p=0.150) or non-fatal stroke (HR=0.90, 95%CI: 0.65-.23, p=0.502).
Results from the secondary endpoint analyses showed a significant reduction in the rate of severe (40%) and nocturnal severe (53%) hypoglycemia with insulin degludec vs. insulin glargine U100 (p<0.001). Severe hypoglycemia was defined as an episode requiring assistance of another person, and nocturnal severe defined as between the hours of 00:01–05:59, inclusive.
Additionally, post hoc analyses showed similar levels of glycemic control with an end of trial A1C estimated treatment difference of 0.01%, (p=0.779) between the two treatment groups and significantly lower fasting plasma glucose levels with insulin degludec after 2 years vs. insulin glargine U100 (estimated treatment difference –7.2 mg/dL, p<0.001).
The safety profile of insulin degludec in DEVOTE was generally consistent with previous insulin degludec clinical trials. In DEVOTE, systematic collection of adverse events was limited to serious adverse events, adverse events leading to permanent discontinuation of investigational product (5.2% of patients in the degludec arm and 5.8% of patients in the glargine U100 arm), medication errors leading to serious adverse events and adverse events related to technical complaints.