SAN DIEGO—Novo Nordisk announced new results published in the New England Journal of Medicine (NEJM) and presented papers at this year’s annual American Diabetes Association’s (ADA) Scientific Sessions from the DEVOTE study.
DEVOTE was the first randomized, double-blind, treat-to-target, event-driven trial comparing two basal insulins, Tresiba (insulin degludec injection 100 U/mL) and insulin glargine U100, in adults with type 2 diabetes at high risk of cardiovascular (CV) diseases. The primary endpoint in DEVOTE was time from randomization to the first occurrence of a three-component composite CV outcome comprising CV death, non-fatal myocardial infarction or non-fatal stroke. Secondary endpoints included severe hypoglycemia, nocturnal severe hypoglycemia, HbA1c and fasting plasma glucose.
“What makes Tresiba superior to other insulin drugs is the way it works, its mechanism of action,” explained Dr. Todd Hobbs, chief medical officer of Novo Nordisk US. “How it is absorbed in the body is unique. It has a flat, long-acting profile for a consistent effect and good control with reduced rates of severe hypoglycemia and no increased risk of major cardiovascular events. The clinical results have shown this.”
He added, “Switching to Tresiba provides significant reductions in blood glucose and lower rates of hypoglycemia in a real-world setting. It has been well received by investigators.”
Tresiba is a once-daily basal insulin that provides a duration of action beyond 42 hours with a flat and stable glucose-lowering effect. It provides low within-day and day-to-day variability and a lower risk of overall, nocturnal and severe hypoglycemia as compared to insulin glargine U100, according to Novo Nordisk. When administration at the same time of day is not possible, Tresiba reportedly enables flexibility in day-to-day dosing time with a minimum of eight hours between injections. Tresiba, which received its first regulatory approval in September 2012, has since been approved in more than 80 countries globally and is now commercially available in more than 50 countries.
The recent clinical trial, which included 7,637 people with type 2 diabetes followed for approximately two years, demonstrated that Tresiba met the primary endpoint of non-inferiority compared with insulin glargine U100 for major adverse CV events (MACE) with a hazard ratio (HR) of 0.91. Findings for each component of MACE were consistent with the primary endpoint, including first occurrence of CV death (HR of 0.96), non-fatal myocardial infarction (HR of 0.85) or non-fatal stroke (HR of 0.90). Results from the secondary endpoints of the trial showed a significant reduction in the rate of severe (40 percent) and nocturnal severe (53 percent) hypoglycaemia with Tresiba vs. insulin glargine U100. Post-hoc analyses showed similar levels of glycemic control with an end-of-trial HbA1c estimated treatment difference of 0.01 percent between the two treatment groups and significantly lower fasting plasma glucose levels with Tresiba after two years vs. insulin glargine U100.
According to Dr. Bernard Zinman of the Lunenfeld-Tanenbaum Research Institute in Toronto, a member of the DEVOTE steering committee, “Risk of cardiovascular disease and hypoglycemia are important concerns for those with type 2 diabetes, and the results from DEVOTE add to the mounting evidence that will play an important role in treatment decisions.”
The safety profile of Tresiba in DEVOTE was generally consistent with previous Tresiba 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 percent of patients in the Tresiba arm and 5.8 percent of patients in the insulin glargine U100 arm), medication errors leading to serious adverse events and adverse events related to technical complaints. Severe hypoglycaemia was defined as an episode requiring assistance of another person, and nocturnal severe defined as between the hours of 00:01-05:59, inclusive.
In another Novo Nordisk development, findings from a post-hoc analysis of the LEADER cardiovascular (CV) outcomes trial showed that treatment with Victoza (liraglutide) resulted in similar reductions in the risk of major cardiovascular events in people with type 2 diabetes at high CV risk, regardless of whether or not they experienced an episode of severe hypoglycemia during the trial. Results were also presented at the American Diabetes Association 77th Scientific Sessions.
Hobbs concluded, “This is a very busy and exciting time with so many projects coming to fruition.”