Investigators tested a new, ultra-long acting insulin product, insulin degludec, and found that it is comparable to insulin glargine U100 regarding cardiovascular safety and is also associated with significant reductions in severe hypoglycemia, they reported during a symposium here at the American Diabetes Association’s 77th Scientific Sessions® at the San Diego Convention Center.
The DEVOTE study was a phase 3, multi-center, international, randomized, double-blind study that was designed to evaluate the relative cardiovascular safety of insulin degludec (IDeg)1 compared with insulin glargine (IGlar) U100 when added to a standard of care regimen for people with type 2 diabetes. IDeg is a new generation, once-daily, injectable basal insulin that provides duration of action for at least 42 hours. IGlar is the most commonly prescribed insulin product for people with type 2 diabetes, and its cardiovascular safety was established through the ORIGIN trial published in 2012.
In the study, researchers evaluated 7,637 people with type 2 diabetes who were at high risk of major adverse cardiovascular events (MACE), for approximately two years. They enrolled patients between October 2013 and November 2014 at 436 sites in 20 countries. Of study participants, 6,506 had prior cardiovascular disease or chronic kidney disease, and the remainder had multiple cardiovascular risk factors. All patients were randomized to receive either injectable daily IDeg or IGlar, in addition to the other medications the patients were already taking. However, neither the patient nor the provider knew which insulin formulation they were receiving/giving, which allowed for a thorough examination of safety and efficacy and is unique for insulin-comparative studies.
The study results confirmed the cardiovascular safety of IDeg compared with IGlar U100 by demonstrating noninferiority of MACE, such as first occurrence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke, occurring with a hazard ratio of 0.91 in favor of IDeg vs IGlar, with no statistically significant differences between the two treatments. The findings of the DEVOTE trial also demonstrated the hypoglycemic benefit of IDeg. Severe hypoglycemia remains the most serious treatment risk related to insulin therapy, and prior studies have suggested that IDeg is associated with a lower risk of hypoglycemia than IGlar U100.
Severe hypoglycemia is defined as an episode of low blood glucose that is severe enough that the patient requires assistance from another person in order to recover. It is the most serious acute complication of insulin treatment and can lead to seizures, coma, or even death. Use of IDeg therapy resulted in 27% fewer patients experiencing an episode of severe hypoglycemia and a 40% overall reduction of total episodes of severe hypoglycemia. Patients in the IDeg-treated group also experienced a 53% reduction in the rate of nocturnal severe hypoglycemia. All severe hypoglycemic events of the study participants during the trial period were evaluated and confirmed by a group of external experts, and the differences were all found to be statistically significant.
“The findings of the DEVOTE study are in line with previous clinical trials comparing insulin degludec to insulin glargine U100, so we are pleased to be able to provide conclusive evidence regarding the safety of insulin degludec for patients with type 2 diabetes who are at high risk of cardiovascular complications,” said study investigator Steven Marso, MD, chief medical officer for HCA Midwest Health cardiovascular services.
“These results will provide reassurance for both people with type 2 diabetes and their health care providers that this new insulin product has comparable cardiovascular safety to IGlar,” said study investigator John Buse, MD, PhD, director of the Diabetes Center, director of the NC Translational and Clinical Sciences Institute, and executive associate dean for clinical research at the University of North Carolina School of Medicine in Chapel Hill. “It is exciting that with IDeg, patients can achieve positive glycemic control along with a major reduction in the risk of severe hypoglycemia, particularly nocturnal severe hypoglycemia.”