Novo Nordisk has announced the full results of the DEVOTE trial investigating the cardiovascular (CV) safety profile of long-acting insulin Tresiba (insulin degludec), in adults with type 2 diabetes (T2D).


The trial results, presented at the 77th annual Scientific Sessions of the American Diabetes Association (ADA), also demonstrated a significantly lower rate of severe hypoglycaemia with insulin degludec treatment compared with insulin glargine U1001. These findings, which are the first to specifically examine the CV impact of insulin degludec, provide further evidence to support its safety profile and are in line with previous studies.

Dr Ponnusamy Saravanan, Associate Clinical Professor and Honorary Consultant Physician in Diabetes, Endocrinology & Metabolism, University of Warwick commented, “There are four million people living with T2D in the UK. Given the increased risk of CV complications associated with T2D, when choosing to initiate therapy it’s increasingly important for clinicians to consider the CV safety of treatments based on the latest data.

DEVOTE is unique as it is the first double-blind head to head insulin trial looking at CV safety. The full findings from DEVOTE provide further evidence supporting Tresiba’s (insulin degludec) CV safety profile.”

Insulin degludec met the primary endpoint of the DEVOTE trial of non-inferiority compared with insulin glargine U100 for major adverse CV events (MACE) with a hazard ratio (HR) of 0.91 (95% confidence interval [CI]: 0.78; 1.06, p=0.209). Additionally, the findings for each component of MACE were consistent with the primary endpoint, including first occurrence of CV death (HR=0.96, 95% CI: 0.76; 1.21, p=0.714), nonfatal myocardial infarction (HR=0.85, 95% CI: 0.68; 1.06, p=0.150) or non-fatal stroke (HR=0.90, 95% CI: 0.65; 1.23, p=0.502).

Results from the secondary endpoints of the trial showed a significant reduction in the rate of severe (40%; 3.70 events/100 patient-years with insulin degludec vs 6.25 events/100 patient-years with insulin glargine U100) and nocturnal severe (53%; 0.65 vs 1.40 events/100 patient-years) hypoglycaemia with insulin degludec vs. insulin glargine U100 (both p<0.001). Additionally, post hoc analyses showed: similar levels of glycaemic control with an end of trial HbA1c 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 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 insulin degludec arm and 5.8% of patients in the insulin glargine U100 arm), medication errors leading to serious adverse events and adverse events related to technical complaints.